Talk:2011 Group 2 Project

From CellBiology

Post Peer Assessment Discussion

Hey guys in response to the peers i moved around my pictures, gave them text under them, and added a lot of new information and some photos to the structure section. the only issue we have left is to clean up our reference list since it mostly looks like a bunch of pubmed IDs. i guess we will ask mark what to do with this.--Michael Orenstein 21:48, 25 May 2011 (EST)

Week 7

  • This is the week before the mid-session break.
  • In the lab this week we will have an opportunity to discuss any issues which are slowing progress on your project.
  • The Thursday of the week beginning 02 May will be when all projects will be open to Peer Assessment.
  • What you have on your page by Thursday of that week will be the content that others in the class will comment upon.

Week 6

  1. I see many groups now have subsection titles for their projects.
  2. Here are some searches: Pubmed search all databases junction | PLoS junction | JCB junction You can now simply put your own search term into each top window.
  3. Now's the time to get your images, movies, media etc uploaded. Biomed central | JCB | JCB Archive | PLoS. Once uploaded you can make a gallery on either your project or discussion page using <gallery>File:name here</gallery> tags with your image files listed between the tags. When you upload project images, add this text as it appears replacing # with your own Group number to the summary information [[Category:2011Project#]].
  4. Shown below are the criteria that will be used to assess your final project.

Group Assessment Criteria

  • The key points relating to the topic that your group was allocated are clearly described.
  • The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
  • Content is correctly cited and referenced.
  • The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.
  • Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
  • Relates the topics and content of the Wiki entry to learning aims of cell biology.
  • Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer’s wiki.
  • Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
  • The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
  • Develops and edits the wiki entries in accordance with this sites wiki guidelines.


By Week 5

Each Group member has added to the discussion page:

  1. A Review Article
  2. A Historic Research Article
  3. A Current Research Article

No two students should add the same paper and there should be a link to the original article.

Improvements

  • structure section needs to be longer
  • make disease headings bigger
  • add frames and legends to pictures
  • fix structure of page integrate pictures and text maybe change headings to different order
  • make referecnes all the same
  • add to glossary and put in alphabetical order

--z3253348 10:17, 19 May 2011 (EST)

Peer assessment

Gap Junctions:

  • Intro is well-written, but too much specific information. You just repeat it all later in the page. Also, I'm not sure if you need to spell out the sections that are on the rest of the page. You can just tell by the headings of the sections.
  • "Structure" and "Function" is concise and well-written. Good images.
  • "Location" is a good section and helps to contextualize gap junction in the body.
  • "Comparison" is a well done section but is it necessary? Also, how are you comparing other junctions with gap junctions like the title says? Maybe you could say how gap junctions are associated with other junctions?
  • "Diseases" nicely formatted section, easy to read, good images.
  • "Current Research" language a little hard to follow sometimes. Maybe try to portray information with less technical language.
  • Overall, nice job. Make sure you go over and correct grammatical errors and typos.

Group 2

  • just to start of with i just wanted to mention that you do not have a title saying gap junction on your page.

references:

  • your first picture called specialized cell junction, does not have a reference.
  • All the images are relevant but not all the images have a description beneath it which would be much more helpful.
  • I like the way you broke down the locations of gap junctions and possible diseases, which made it easier to read.
  • the glossary section could be longer. It would also be easier to read if the glossary is in alphabetical order.


GROUP 2: Gap Junctions


The layout and format of the web page could be better and I am saying this because when you add the picture straight under the text it takes up a large amount of space and the web page looks longer than it really is. However the subheading and the information had a really good flow. The tables in the section, especially the table describing the different types of junction allow you to highlight certain points. The images that you have on your webpage are really well explained yet as a criticism you could have more pictures. The page has an extremely scientific feel so you don’t have to change anything there. There are some spelling mistakes but that shouldn’t be a big problem as you will probably find these in your final check. I really found informative but is sort of thought that maybe if somebody without a background in science would struggle certain parts. Putting it under different sub headings also made this extremely easy to follow as well but all in all I really liked the page. Nice Work!!!


Group 2

  • Introduction: It goes too in depth.Details about different groups should go to classification.In this part , you also talk about the details of the molecular constituents of gap junctions , which is kinda off the objective of introduction.

This part should have a brief talk on the roles or importance of gap junctions to organisms ,formation and its location, so that readers can have a broad idea what it is before going further down.

  • History: Too long.
  • Structure and functional roles: They are alright.
  • Location: Details in this part can be put under functional roles, so you wont have 2 duplicated kinda subheadings.
  • Comparing with other junctions: It is a good idea.
  • Disease associated : Details are well organised in disease associated part , and nice images .
  • Research: It is alright .
  • Glossary: It should be in alphabetical order.


Group 2-Gap Junction

  • Intro – very good introduction as it gives an overview of different type of junctions. The description of the composition and different types of gap junctions is very clear in this section. Good choice of pictures, very easy to interprete.
  • History – this section is very thoroughly done, great work!
  • Structure – Description is logical and easy to follow, however more detailed information regarding connexins and what they are made of may be desirable.
  • Functional role of gap junctions – How does the different types of connexin affect their function and specialization? At the end of the section you mendtioned that it’s due to the different types and properties of connexins and their expressions, would a more detailed decription on that be good?
  • Location – Good descriptions. More pictures on specific strctures (eg intercalated disks instead of a pic of whole heart) would be good.
  • Comparison – don’t think this table of comparison is really necessary.
  • The last two sections are very well written. Glossary part should be expanded by including more words such as oligodendricytes, cochlea etc.

Group 2

The inclusion of very specific knowledge shows that the page is well researched and gives the right amount of detail to the reader. There are a variety of interesting pictures, from diagrams to photographs, all which add to the page. The pictures throughout the page need captions so there is a small amount of info about that picture actually with the picture on the page itself. The table of comparisons is a good idea, however I am not sure how much can be learnt about gap junctions themselves. It seems to take up too much of the page proportionally with a lot of information that seems best suited elsewhere. Despite this, the clear advantage of such a table is that it allows the page to not only be a resource for gap junctions, but as a starting point for learning about other types of junctions. This is very helpful for students looking for further knowledge not specific to the gap junctions themselves.


Group 2

Good work group 2. It was a good read but is it really necessary to discuss the other junctional structures in that depth? Also there are alot of points you could elaborate on such as:

- structure of the gap junction (this section seems too brief)

-The functional role (the 4 points you mentioned i.e. 1) Transmission of excitation in cardiac muscle, smooth muscle and central nervous system (CNS) neurons...etc)

also, for the diseases section, it would be better if you could make the headings for the types of diseases bigger so that people wouldnt get confused.

Otherwise, an overall good page! :)


GROUP 2 REVIEW

  • All images need a link to where they came from in them. Also maybe make some images thumbnails as they don't need to be as big (ie. Connexins image, hexagonal gap junctions)
  • Introduction: Nice introduction
  • History: Very thorough though images should be used to break up text rather than thrown in at bottom of section.
  • Structure: The info here is a little too concise, don't be afraid to explain what you are talking about. ie. maybe explain what passes through the junction and why.
  • Functional Role of Gap junctions: Well researched and good use of bold for main points.
  • Location: Good inclusion of heading though should probably go before or after Structure.
  • Comparison with other junctions: Nice Table - maybe link the titles to the other topic pages that they are talking about
  • Disease associated with Gap Junctions: Good clear format of text and diseases though the images should go AROUND the text not just under it. Too much white!
  • Current: GREAT.
  • Glossary: You just need to Alphabetise this and maybe add some more.

Group 2- Gap Junctions

  • Good introduction.
  • The text is balanced well enough with the photos.
  • The only thing now is to get rid of empty spaces.
  • History is good and referenced properly.
  • Electron micrograph filtered image belongs to history or is something else??
  • Bold text draws the attention and the reader knows what is going next.
  • The table with other junction is good.
  • Structure needs more to be done.
  • Function is good.
  • Diseases part is good and well-linked with the abnormalities of the junction.
  • Glossary is short.
  • Good headings and sub-headings.
  • Overall,good work.

Gap Junction pro 2

  • Introduction clearly introduces the topic and its constituents

it is a perfect introduction.

  • History is good but seems too comprehensive.

Structure might benefit from simplification and a table

  • A good choice of diagrams and headings
  • Citation is comprehensive and a visible amount of research has gone into the project
  • Images need more work on the image content description
  • alphebetise glossary
  • Disease section is well put togetther with good images and content
  • overall the project does conform with the wiki page as teaching strategy, however its a little long too much similar type of information.
  • editing and peer communication is evident


Gap junction - group 2

I really like the balance between pictures and texts , obviously the photos compensate each section beautifully. Even before reading the project page , the history section is way too long. In the function of the gap junction the hand-drawn image by student was outstanding . The table is beautifully done however, the text should be in bullet points for easier understanding (with more colors on the table). The examples of diseases given were broad and appropriated. The use of pictures in each disease subheadings was very appropriate. The glossary , in comparison to the page are relatively small . The references needs to be fixed up for all the pub med links. Hundreds references used represented the indept research that had been carried out . Good job guys


Group 2- Gap Junctions

  • My First impression is that you have a good text/image ratio.
  • Your introduction is very clear and it is helpful for me that you have outlined what you will be doing in the rest of your project so that I know what to expect.
  • Dot points and bold text make it easy to see the important details
  • Comparing gap junctions with other junction types is an awesome idea and helps understand the unique features of your junction type
  • The only thing that I can comment on negatively is that the structure function section, which technically should be the largest part, is small compared to the rest of the project.


Group 2

  • The introduction gave a good overview of all junctions which gives a good idea of what a junction is before detailing specifically what a gap junction is.
  • Detailed history shows good research.
  • Good array of pictures throughout the whole page, breaks up the information well.
  • Comparison table is very detailed and shows a good amount of research as well as the diseases section which is very interesting especially with the addition of pictures.
  • Glossary needs to be added to.
  • The choice of content, headings and sub-headings, diagrams and tables show a good understanding of the topic area.


Overall, a great effort can be seen from the Page. However, I have some points that might be useful to improve the page: 1.Introduction Section: the photos are not titled, and the second photo with channels is slightly big, it might look better with a smaller version. 2.History shows lots of information, and the group has done more than enough research. It looks long. 3.The em Photos in the History Section could be moved to the Structure. 4.Functional role, location and comparison, I don’t see how it can be improved, because I like the balance between photos and words. Well done. 5.Photos in “ Diseases Associated with Gap junctions could be moved to the right or left so they don’t take too much space in the page.

Gap Junctions

  • Really good set out, nice and organized, making it easy to read
  • The history is really long and detailed. There’s a lot of really good information in it, but it could be a bit better if only the really important bits were outlined. Of course, this isn’t a very big criticism as you can’t really have too much information.
  • Good description of the structure. Could you note differences between human gap junctions and their homologues in plants?
  • Good incorporation of KO mice in explaining the function of Cx32
  • I like how you’ve done the locations of gap junctions, well structured
  • It’s a good idea to give a comparison with the other junctions. The table is nice, but since you’re not doing the other junctions do you need that much detail? You could always make links to the other pages or something
  • Good variety of abnormalities and nice, brief descriptions
  • Nice incorporation of the really recent research, show’s how up to date your information is
  • Overall a really good page. Nice work!

Group 2

  • I’m starting to wonder if it’s just my browser, because I can’t see a main “Gap Junctions” title.
  • Intro is fairly cohesive, describes topic well and is easy to understand. “Connexins (Cx) are named after their molecular weight and they are tissue-specific and even cell-specific which represent that some connexins are prominently expressed only in a few tissues and some, like Cx43 being more prevalent”- I think I understand what you’re trying to say but it needs rewording. Likewise with a few other sentences in intro.
  • Few typos but that’s to be expected!
  • I actually like that the history is so long. It gives the reader a more comprehensive understanding of gap junctions instead of just being a chronological list of random facts.
  • I think the structure section is the most well written section. It’s concise and effectively gets the info across.
  • Some interesting info in functional role. Perhaps there is a reason you haven’t included this, but I’d be interested to know what the “special permeability characteristics” are that are characteristic of heterotypic junctions.
  • Location- I think this is an excellent section to have! Gave me a well rounded understanding of the significance of gap junctions
  • I’m not entirely sure that the comparison table is necessary considering that the junctions are covered by other groups. Having said that, it shows initiative, and a good understanding of intercellular interactions, so that can’t be a bad thing, right?


2)

• The page goes very in depth into the topic showing a great understanding of it.

• Comparisons done using the table with other junction and the use of sub headings gave a great flow to the page. This allowed for an easier understanding of the content for someone using it as a learning tool.

• The pictures in the disease section are used very well and tie into the area. The way they are used to space the individual deiseases apart makes the section easy to digest and take in.

• The only thing that looks out of place are the pictures in the structure section, maybe place them to the side of the text so they aren’t disconnected from it.

• Some stats and treatments for the disease section can be added.

• Glossary could use more content.



Group 2: Gap Junctions

Introduction: The introduction is very clear and explains both the topic and what your article details.

History: The pictures below the history, could adjoin a specific entry so that the reader can see how they directly relate to the history. Whilst the pictures themselves are good, at the moment it is a little unclear how the pictures extend on what is being said in the history section. However the written content of the history is informative, covering both discovery up till very recent times. This overview is well done.

Structure: A brief structure, or explanation of the difference between the various connexins mentioned in the next two sections would be helpful.

Location And Comparison with Other Junctions: These are both helpful sections, that add more accessibility to the page by giving the reader more information about gap junctions and their context.

Glossary: The glossary could be alphabetised for ease of use.

Note: Uploading some of your own drawings would be helpful.


--Mark Hill 17:07, 30 March 2011 (EST) OK Group 2, Just one student contributing sub-headings to date and no other content has been added to either your discussion or project page. You were meant to have already begun looking into both the topic and references, pasting links on your discussion page. I will see you in the lab tomorrow to discuss whether you are having problems or are simply not doing the work. This search should get you started. Search Pubmed: Gap Junction

Discussion

Guys, I've uploaded my disease stuff except i'm having problems with uploading the references and pictures. WIll try again later. I've also added a few things to our glossary. Anyway hope you've all had a good break!

--Elizabeth Blanchard 10:28, 30 April 2011 (EST)

I found another article concerning disease that might be of use:

Gap-Junction Channels Dysfunction in Deafness and Hearing Loss

I wouldn't put the abstract since it's too long.

[1]

--z3283837 23:00, 26 April 2011 (EST)

Hey guys, I am kind of finished with my part for the intro and the function although it needs a little bit of touch up. Anyway, while researching, I just found a few review articles that might be helpful. Whoever is doing the location of gap junctions, this article below gives you an overview of the expression patterns of different connexins in different tissues.

Diversity and properties of connexin gap junction channels

Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells and provide a direct pathway for electrical and metabolic signaling between adjacent cells. The family of connexin genes comprises 20 members in the mouse and 21 genes in the human genome. Connexins are expressed in all tissues except differentiated skeletal muscle, erythrocytes, and mature sperm cells. Various tissues express more than one type of connexins; therefore, homotypic, heterotypic, and heteromeric gap junction channels may form between cells. In this article, we briefly review basic gating and permeability properties of homotypic and heterotypic gap junction channels as well as recent achievements in the research of their regulation by transjunctional voltage, intracellular calcium, pH, and phosphorylation. [2]

Another review article mention about the mutations in certain connexins leading to some diseases so it might be helpful with the disease section of our project. Here is the article:

Diverse functions of vertebrate gap junctions

Gap junctions are clusters of intercellular channels between adjacent cells. The channels are formed by the direct apposition of oligomeric transmembrane proteins, permitting the direct exchange of ions and small molecules (< 1 kDa) between cells without involvement of the extracellular space. Vertebrate gap junction channels are composed of oligomers of connexins, an enlarging family of proteins consisting of perhaps > 20 members. This article reviews recent advances in understanding the structure of intercellular channels and describes the diverse functions attributable to gap junctions as a result of insights gained from targeted gene disruptions in mice and genetic disease in humans. [3]

Finally, there's this cartoon image on structure of connexin that you may be able to reuse, but it's worthwhile to look at.

A fully atomistic model of the Cx32 connexon

Connexins are plasma membrane proteins that associate in hexameric complexes to form channels named connexons. Two connexons in neighboring cells may dock to form a "gap junction" channel, i.e. an intercellular conduit that permits the direct exchange of solutes between the cytoplasm of adjacent cells and thus mediate cell-cell ion and metabolic signaling. The lack of high resolution data for connexon structures has hampered so far the study of the structure-function relationships that link molecular effects of disease-causing mutations with their observed phenotypes. Here we present a combination of modeling techniques and molecular dynamics (MD) to infer side chain positions starting from low resolution structures containing only C alpha atoms. We validated this procedure on the structure of the KcsA potassium channel, which is solved at atomic resolution. We then produced a fully atomistic model of a homotypic Cx32 connexon starting from a published model of the C alpha carbons arrangement for the connexin transmembrane helices, to which we added extracellular and cytoplasmic loops. To achieve structural relaxation within a realistic environment, we used MD simulations inserted in an explicit solvent-membrane context and we subsequently checked predictions of putative side chain positions and interactions in the Cx32 connexon against a vast body of experimental reports. Our results provide new mechanistic insights into the effects of numerous spontaneous mutations and their implication in connexin-related pathologies. This model constitutes a step forward towards a structurally detailed description of the gap junction architecture and provides a structural platform to plan new biochemical and biophysical experiments aimed at elucidating the structure of connexin channels and hemichannels. [4]

--z3283837 21:11, 26 April 2011 (EST)

Michael the history looks fantastic! do u remeber where u put that retina article i cant find it.. --z3253348 18:34, 23 April 2011 (EST)

Hey guys hope your break is going well. I just finished the "History" segment of our project and I posted it on the group page. Since we are having some issues with our discussion page, i figured rather than repost all the references here you can just use the ones on our group page. A lot of those articles are relevant to other topics such as function and disease of gap junction so when you are reading through the history of gap junctions, if any of those points have to due with your topic you should definetely go check out the article on Pubmed. Liz I know you are doing diseases so if you look in some of the later years i posted some stuff on the history of the diseases. Whoever is doing function, there is a bunch of information on function of gap junctions. just read the titles of my references and if it seems helpful, check out the article.

--Michael Orenstein 11:06, 23 April 2011 (EST)


Whoever is doing FUNCTION this article may be helpful for you

Control of intercellular communication by voltage dependence of gap junctional conductance.

Abstract

The junctional conductance between coupled amphibian blastomeres exhibits a high degree of voltage dependence, as previously described in voltage clamp studies (Spray, D.C., A.L. Harris, and M.V.L. Bennett (1981) J. Gen. Physiol. 77: 77-95; Harris, A.L., D.C. Spray, and M.V.L. Bennett (1981) J. Gen. Physiol. 77: 95-117). The present study examines the properties which this voltage dependence confers on electrotonic coupling between cells. The effects of applied pulses and ramps of current are studied experimentally and are modeled by calculation. During sufficiently large current pulses applied to one cell of a pair, the cells uncouple and then recouple after termination of the pulses. Ramps of current applied to one of the cells can give voltage-current (V-I) relations with a region of hysteresis within which the cells are stably coupled or stably uncoupled depending on previous history. Intrinsically generated currents are able to cause bistability of coupling in the absence of externally applied current. Calculations from the parameters of junctional conductance defined under voltage clamp fully account for these findings and illustrate how junctional and nonjunctional conductances affect the V-I relations in the region of bistability. Recordings from several cells within a small group show that boundaries of intercellular communication can be altered by applied current, a finding that also can be accounted for by voltage dependence of junctional conductance. The "Appendix" examines quantitatively the criteria required for bistability of coupling and the relevance of bistability for intercellular signaling. The plasticity of coupling which the voltage dependence of junctional conductance confers on cells offers an intriguing mechanism by which patterns of intercellular communication could be determined and changed in developing tissues.

[5]

--Michael Orenstein 11:06, 23 April 2011 (EST)

Hey Liz i found this article whihc may be helpful to you for diseases

Mechanisms of gap junction traffic in health and disease.

Abstract

Gap junctions (GJs) allow direct communication between cells. In the heart, GJs mediate the electrical coupling of cardiomyocytes and as such dictate the speed and direction of cardiac conduction. A prominent feature of acquired structural heart disease is remodeling of GJ protein expression and localization concomitant with increased susceptibility to lethal arrhythmias, leading many to hypothesize that the two are causally linked. Detailed understanding of the cellular mechanisms that regulate GJ localization and function within cardiomyocytes may therefore uncover potential therapeutic strategies for a significant clinical problem. This review will outline our current understanding of GJ cell biology with the intent of highlighting cellular mechanisms responsible for GJ remodeling associated with cardiac disease.

[6]

--Michael Orenstein 11:06, 23 April 2011 (EST)

hey everyone, I have thought of some headings for our assignment let me know which you think are most suitable

(1) Introduction - just a quick summary - Hailey

(2) Discovery/History - who discovered gap junctions - Michael

(3) Structure - what they look like/how they are formed - Michael

(4) Function(importance) - their job - Hailey

(5) Location - where they are found - Hadassah

(6) Comparison - briefly explain how our junction is different from others - Hadassah

(7) Diease - possibly something to do with dieases associated with abnormalties of the junction - Elizabeth

(8) Research - current research of gap junctions/new research and discoveries - Elizabeth

--z3253348 20:19, 29 March 2011 (EST)


Headings seem all good. We should try and organize who is going to do what at some point too.

[7]

Abstract

Intercellular channels present in gap junctions allow cells to share small molecules and thus coordinate a wide range of behaviors. Remarkably, although junctions provide similar functions in all multicellular organisms, vertebrates and invertebrates use unrelated gene families to encode these channels. The recent identification of the invertebrate innexin family opens up powerful genetic systems to studies of intercellular communication. At the same time, new information on the physiological roles of vertebrate connexins has emerged from genetic studies. Mutations in connexin genes underlie a variety of human diseases, including deafness, demyelinating neuropathies, and lens cataracts. In addition, gene targeting of connexins in mice has provided new insights into connexin function and the significance of connexin diversity.


[8]

Abstract

Gap junctions are specialized membrane domains composed of collections of channels that directly connect neighboring cells providing for the cell-to-cell diffusion of small molecules, including ions, amino acids, nucleotides, and second messengers. Vertebrate gap junctions are composed of proteins encoded by the "connexin" gene family. In most cases examined, connexins are modified post-translationally by phosphorylation. Phosphorylation has been implicated in the regulation of gap junctional communication at several stages of the connexin "lifecycle", such as the trafficking, assembly/disassembly, degradation, as well as, the gating of gap junction channels. Since connexin43 (Cx43) is widely expressed in tissues and cell lines, we understand the most about how it is regulated, and thus, connexin43 phosphorylation is a major focus of this review. Recent reports utilizing new methodologies combined with the latest genome information have shown that activation of several kinases including protein kinase A, protein kinase C, p34(cdc2)/cyclin B kinase, casein kinase 1, mitogen-activated protein (MAP) kinase and pp60(src) kinase can lead to phosphorylation at 12 of the 21 serine and two of the six tyrosine residues in the C-terminal region of connexin43. In several cases, use of site-directed mutants of these sites have shown that these specific phosphorylation events can be linked to changes in gap junctional communication.

References

  1. J P Binet Pioneering in heterografts. Ann. Thorac. Surg.: 1989, 48(3 Suppl);S71-2 PubMed 2673109
  2. Mindaugas Rackauskas, Vaidas Neverauskas, Vytenis Arvydas Skeberdis Diversity and properties of connexin gap junction channels. Medicina (Kaunas): 2010, 46(1);1-12 PubMed 20234156
  3. A M Simon, D A Goodenough Diverse functions of vertebrate gap junctions. Trends Cell Biol.: 1998, 8(12);477-83 PubMed 9861669
  4. Sergio Pantano, Francesco Zonta, Fabio Mammano A fully atomistic model of the Cx32 connexon. PLoS ONE: 2008, 3(7);e2614 PubMed 18648547
  5. A L Harris, D C Spray, M V Bennett Control of intercellular communication by voltage dependence of gap junctional conductance. J. Neurosci.: 1983, 3(1);79-100 PubMed 6822860
  6. Geoffrey G Hesketh, Jennifer E Van Eyk, Gordon F Tomaselli Mechanisms of gap junction traffic in health and disease. J. Cardiovasc. Pharmacol.: 2009, 54(4);263-72 PubMed 19701097
  7. T W White, D L Paul Genetic diseases and gene knockouts reveal diverse connexin functions. Annu. Rev. Physiol.: 1999, 61;283-310 PubMed 10099690
  8. Paul D Lampe, Alan F Lau The effects of connexin phosphorylation on gap junctional communication. Int. J. Biochem. Cell Biol.: 2004, 36(7);1171-86 PubMed 15109565

--Elizabeth Blanchard 23:10, 30 March 2011 (EST)

Hey guys, I also think we should talk about how gap junctions function differently within different cells of the body. They may all act the same but if we research it and find thats not the case then maybe thats something we should take note of. also below i've added 2 abstracts to 2 pubmed articles concerning gap junctions

Connexins and the gap in context.

Mroue RM, El-Sabban ME, Talhouk RS.

Division of Life Sciences, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.

Abstract

Gap junctions (GJ) can no longer be thought of as simple channel forming structures that mediate intercellular communication. Hemi-channel and channel-independent functions of connexins (Cxs) have been described and numerous Cx interacting partners have been uncovered ranging from enzymes to structural and scaffolding molecules to transcription factors. With the growing number of Cx partners and functions, including well-documented roles for Cxs as conditional tumor suppressors, it has become essential to understand how Cxs are regulated in a context-dependent manner to mediate distinct functions. In this review we will shed light on the tissue and context-dependent regulation and function of Cxs and on the importance of Cx-interactions in modulating tissue-specific function. We will emphasize how the context-dependent functions of Cxs can help in understanding the impact of Cx mis-expression on cancer development and, ultimately, explore whether Cxs can be used as potential therapeutic targets in cancer treatment. In the end, we will address the need for developing relevant assays for studying Cx and GJ functions and will highlight how advances in bioengineering tools and the design of 3D biological platforms can help studying gap junction function in real time in a non-intrusive manner. [1]

Gap junctions and connexins as therapeutic targets in cancer.

Kandouz M, Batist G.

Wayne State University, Department of Pathology, 5101 Cass Avenue, Chemistry Building, Detroit, Michigan 48202, USA. ag1764@wayne.edu

Abstract

IMPORTANCE OF THE FIELD: Connexins (Cxs) and gap junctional intercellular communications (GJICs) play roles in cancer development, growth and metastasis. Experimental studies suggest that targeting Cxs may be a novel technique, either to inhibit tumor cell growth directly or to sensitize to various therapies.

AREAS COVERED IN THIS REVIEW: A brief introduction to the role of Cxs in cancer. The focus is mainly on data available in the literature regarding therapeutic aspects.

WHAT THE READER WILL GAIN: This article reviews the various strategies that take advantage of gap junctions and connexins to eliminate cancer cells, including use of the bystander effect (BE) in gene therapy, the effect of connexins on chemosensitization, the role of apoptotic processes and interactions with the microenvironment. Attempts to restore connexin expression at the transcriptional and post-transcriptional levels are described, as well as promising strategies recently explored. The potential and limitations of the approaches are discussed.

TAKE HOME MESSAGE: Connexins have multiple facets, singly, in hemichannel complexes, in gap junctions or interacting with different proteins. The regulation of their expression is not fully resolved and selective manipulation of Cxs expression is therefore a challenge. Although the therapeutic potential of connexins is undeniable, more effort is needed to study the regulation and functions of these proteins. [2]

References

  1. R M Mroue, M E El-Sabban, R S Talhouk Connexins and the gap in context. Integr Biol (Camb): 2011, 3(4);255-66 PubMed 21437329
  2. Mustapha Kandouz, Gerald Batist Gap junctions and connexins as therapeutic targets in cancer. Expert Opin. Ther. Targets: 2010, 14(7);681-92 PubMed 20446866

Hey guys so i put some names under the headings that we just discussed. we shoudl still all look for articles and read up on gap junctions and then we can always change our roles if we want

--Michael Orenstein 01:15, 31 March 2011 (EST)


[1]

Abstract Gap junctions consist of arrays of intercellular channels composed of integral membrane proteins called connexin in vertebrates. Gap junction channels regulate the passage of ions and biological molecules between adjacent cells and, therefore, are critically important in many biological activities, including development, differentiation, neural activity, and immune response. Mutations in connexin genes are associated with several human diseases, such as neurodegenerative disease, skin disease, deafness, and developmental abnormalities. The activity of gap junction channels is regulated by the membrane voltage, intracellular microenvironment, interaction with other proteins, and phosphorylation. Each connexin channel has its own property for conductance and molecular permeability. A number of studies have tried to reveal the molecular architecture of the channel pore that should confer the connexin-specific permeability/selectivity properties and molecular basis for the gating and regulation. In this review, we give an overview of structural studies and describe the structural and functional relationship of gap junction channels.

Conclusion Since its discovery in the 1960s, structural studies of the gap junction channel have been performed extensively.

References

  1. Shoji Maeda, Tomitake Tsukihara Structure of the gap junction channel and its implications for its biological functions. Cell. Mol. Life Sci.: 2011, 68(7);1115-29 PubMed 20960023

--z3253348 11:58, 31 March 2011 (EST)


Here are the three articles related to gap junctions respectively: Review article, Historic Research article and Current Research article.


Structural and functional studies of gap junction channels (Review Article)

Abstract [1] X-ray analysis of the human connexin26 gap junction channel has provided structural details of its open state. The gap junction channel is formed by paired hemichannels on two adjacent cells; each hemichannel consists of six protomers, and exhibits a six-fold symmetry. The protomer folds in a typical four-helix bundle. The amino-terminal region folds in a short helix and is inserted into the lumen to form a funnel structure. The structure of the amino-terminal region could explain the channel's gating mechanism. Extensive interactions between two hemichannels allow the gap junction channel to tightly connect two adjacent cells. The gap junction, which consists of hundreds of gap junction channels, could both serve as an intracellular channel and contribute to cellular adhesion.


Variations in tight and gap junctions in mammalian tissues (Historic Research Article)

Abstract [2] The fine structure and distribution of tight (zonula occludens) and gap junctions in epithelia of the rat pancreas, liver, adrenal cortex, epididymis, and duodenum, and in smooth muscle were examined in paraformaldehyde-glutaraldehyde-fixed, tracer-permeated (K-pyroantimonate and lanthanum), and freeze-fractured tissue preparations. While many pentalaminar and septilaminar foci seen in thin-section and tracer preparations can be recognized as corresponding to well-characterized freeze-fracture images of tight and gap junction membrane modifications, many others cannot be unequivocally categorized-nor can all freeze-etched aggregates of membrane particles. Generally, epithelia of exocrine glands (pancreas and liver) have moderate-sized tight junctions and large gap junctions, with many of their gap junctions basal to the junctional complex. In contrast, the adrenal cortex, a ductless gland, may not have a tight junction but does possess large gap junctions. Mucosal epithelia (epididymis and intestine) have extensive tight junctions, but their gap junctions are not as well developed as those of glandular tissue. Smooth muscle contains numerous small gap junctions The incidence, size, and configuration of the junctions we observed correlate well with the known functions of the junctions and of the tissues where they are found.


Autophagy: a pathway that contributes to connexin degradation (Current Research Article)

Abstract [3] The function of connexins, which form gap junctions, can be rapidly modulated by degradation, because they have half-lives of only a few hours. Autophagy is a degradation pathway that has been implicated in several diseases and can be induced by cellular stresses such as starvation. We investigated the involvement of autophagy in proteolysis of the wild-type connexins CX50 and CX43, and a cataract-associated connexin mutant, CX50P88S, which forms cytoplasmic accumulations. We observed that cytoplasmic connexins were partially (cup-shaped) or completely (ring-shaped) enclosed by structures containing the autophagy-related protein LC3. Intracellular connexins also colocalized with p62, a protein that might serve as a cargo receptor for autophagic degradation. Starvation induced a decrease in connexin levels that was blocked by treatment with chloroquine, a lysosomal protease inhibitor, or by knockdown of the autophagy-related protein Atg5. These results demonstrate that autophagy can regulate cellular levels of wild-type connexins and imply that the persistence of accumulations of CX50P88S results from insufficient degradation capacity of constitutive autophagy.


References

  1. So Nakagawa, Shoji Maeda, Tomitake Tsukihara Structural and functional studies of gap junction channels. Curr. Opin. Struct. Biol.: 2010, 20(4);423-30 PubMed 20542681
  2. D S Friend, N B Gilula Variations in tight and gap junctions in mammalian tissues. J. Cell Biol.: 1972, 53(3);758-76 PubMed 4337577
  3. Alexandra Lichtenstein, Peter J Minogue, Eric C Beyer, Viviana M Berthoud Autophagy: a pathway that contributes to connexin degradation. J. Cell. Sci.: 2011, 124(Pt 6);910-20 PubMed 21378309

--z3283837 15:54, 2 April 2011 (EST)


Hey everyone these articles looked interesting although the recent research article was quite a hard read. I couldn't find much on the location of gap junctions maybe I wasn't typing in the right key words. please post something if you find it. I seemed to find lots of diseases so liz that should be useful for you.


Gap junction remodeling in heart failure. Review Article

Abstract [1] Gap junctions, clusters of transmembrane channels that link adjoining cells, mediate myocyte-to-myocyte electrical coupling and communication. The component proteins of gap junction channels are termed connexins, and gap-junctional channels composed of different connexin types exhibit different biophysical properties. In common with other tissues, the heart expresses multiple connexin isotypes. Spatially defined patterns of expression of 3 connexin isotypes-connexin43, connexin40, and connexin45-form specific cell-to-cell conduction pathways for the spread of current flow that governs the normal cardiac rhythm. Remodeling of gap junction organization and connexin expression is a conspicuous feature of human congestive heart failure and other cardiac conditions in which there is an arrhythmic tendency. This remodeling may take the form of disturbances in the distribution of gap junctions, in which the normal ordered pathways for cell-to-cell conduction are disrupted, or quantitative alterations in connexin expression, notably reduced connexin43 levels, which may contribute to slowing of conduction. Recent evidence from studies in experimental animals strengthens the case that gap junction remodeling is a key determinant of the proarrhythmic substrate in the diseased heart.


Functional analysis of hemichannels and gap-junctional channels formed by connexins 43 and 46. Current Research Article

Abstract [2] The gap junctions (GJs) mediating direct cell-cell interaction are formed by clusters of membrane-spanning proteins known as connexins (Cxs). These channels play a key role in signal transmission, and their permeability, time-, and voltage-dependence are governed by the properties of the specific Cxs forming the gap junctions. Retinal pigment epithelium (RPE) cells express Cx43 and Cx46. Here, we employed a heterologous expression system to explore the functional properties of the hemichannels and GJs that could be formed by different combinations of these Cxs. Specifically, we examined the response kinetics of GJs formed by pairing cells expressing Cx43 or Cx46, or those expressing both, i.e., designated as Cx43*Cx46.


Loss and reappearance of gap junctions in regenerating liver. Historic Research Article

Abstract [3] Changes in intercellular junctional morphology associated with rat liver regeneration were examined in a freeze-fracture study. After a two-thirds partial hepatectomy, both gap junctions and zonulae occludentes were drastically altered. Between 0 and 20 h after partial hepatectomy, the junctions appeared virtually unchanged. 28 h after partial hepatectomy, however, the large gap junctions usually located close to the bile canaliculi and the small gap junctions enmeshed within the strands of the zonulae occudentes completely disappeared. Although the zonulae occludentes bordering the bile canaliculi apparently remained intact, numerous strands could now be found oriented perpendicular to the canaliculi. In some instances, the membrane outside the canaliculi was extensively filled with isolated junctional strands, often forming very complex configurations. About 40 h after partial hepatectomy, very many small gap junctions reappeared in close association with the zonulae occludentes. Subsequently, gap junctions increased in size and decreased in number until about 48 h after partial hepatectomy when gap junctions were indistinguishable in size and number from those of control animals. The zonulae occludentes were again predominantly located around the canalicular margins. These studies provide further evidence for the growth of gap junctions by the accretion of particles and of small gap junctions to form large maculae.

References

  1. Nicholas J Severs Gap junction remodeling in heart failure. J. Card. Fail.: 2002, 8(6 Suppl);S293-9 PubMed 12555135
  2. Quan V Hoang, Haohua Qian, Harris Ripps Functional analysis of hemichannels and gap-junctional channels formed by connexins 43 and 46. Mol. Vis.: 2010, 16;1343-52 PubMed 20664797
  3. A G Yee, J P Revel Loss and reappearance of gap junctions in regenerating liver. J. Cell Biol.: 1978, 78(2);554-64 PubMed 690179

--z3253348 19:41, 4 April 2011 (EST)

Diversity and properties of connexin gap junction channels.[1] (Review Article)

Abstract: Gap junction channels are composed of two apposing hemichannels (connexons) in the contiguous cells and provide a direct pathway for electrical and metabolic signaling between adjacent cells. The family of connexin genes comprises 20 members in the mouse and 21 genes in the human genome. Connexins are expressed in all tissues except differentiated skeletal muscle, erythrocytes, and mature sperm cells. Various tissues express more than one type of connexins; therefore, homotypic, heterotypic, and heteromeric gap junction channels may form between cells. In this article, we briefly review basic gating and permeability properties of homotypic and heterotypic gap junction channels as well as recent achievements in the research of their regulation by transjunctional voltage, intracellular calcium, pH, and phosphorylation.

I feel like this article will be helpful since it talks about the diversity of gap junctions. It mentions how different tissues express different types of connexins so maybe this article will be helpful to whoever ends up doing locations of gap junctions.

Gap junctions and B-cell function.[2] (Historic Research Article)

Abstract: The development of gap junctions between pancreatic B-cells was quantitatively assessed in freeze-fracture replicas of isolated rat islets under various conditions of insulin secretion. Stimulation of insulin secretion by glucose in vitro and by glibenclamide in vivo raised the number of gap junctions between B-cells; glibenclamide alone caused an increase in the size of individual gap junctions. In addition, gap junctions of control and stimulated B-cells showed a packing of particles different from that observed under experimental conditions causing functional uncoupling. The results suggest that gap junctions (and probably coupling) are involved in the secretory activity of B-cells.

This one was helpful because it discussed how gap junctions are involved in the immune response. itd be interesting to read a more recent version of this topic since this one is from 1980.

Alteration of connexin expression is an early signal for chronic kidney disease.[3] (Current Research Article)

Abstract: Chronic kidney disease is promoted by a variety of factors that induce chronic inflammation and fibrosis. Inflammation and excessive scaring have been recently associated with disruptions of the gap junction-mediated intercellular communication. Nevertheless little is known about alterations of the expression of gap junction proteins such as connexin (Cx) 43 and 37 in chronic renal disease. In this study we investigated the expression of these two Cxs in the hypertensive RenTg mice, the anti-glomerular basement membrane glomerulonephritis and the unilateral ureteral obstruction models, all leading to the development of chronic kidney disease in mice. Expression of Cx43 was almost negligible in the renal cortex of control mice. In contrast, Cx43 was markedly increased in the endothelium of peritubular and glomerular capillaries of the 3 month-old RenTg mice, in the glomeruli of mice suffering from glomerulonephritis and in the tubules after obstructive nephropathy. The Cx43 expression pattern was paralleled closely by that of the adhesion markers such as vascular cell adhesion molecule-1 and inter-cellular adhesion molecule-1 as well as the inflammatory biomarker monocyte chemoattractant protein-1. In contrast, Cx37 that was abundantly expressed in the renal cortex of healthy mice was markedly decreased in the three experimental models. Interestingly, Cx43+/- mice showed restricted expression of VCAM-1 after 2 weeks of obstructive nephropathy. These findings suggest the importance of Cxs as markers of chronic renal disease, and indicate that these proteins may participate in the inflammatory process during the development of this pathology

This article is great for whoever ends up doing pathologies associated with gap junctions. it was a bit tough to read but i definetly think there were some quality general points made. it seems as though there are a lot of diseases associated with gap junctions so maybe our best bet it to list a bunch of them and then go into a bit of detail with some of the major, more interesting ones.

I also found this article which i thought would be helpful for whoever writes about gap junction structure. The only issue is that the article is from 1977 so perhaps there had been more structural discoveries. Either way, this would be good for whoever ends up doing history of gap junctions since they could compare and contrast if the structure is indeed different.

Structural diversity of gap junctions. A review.[4]

Abstract:Gap junctions are plasma membrane specializations characterized as aggregates of intramembranous particles in two apposed membranes meeting particle-to-particle in the 2-4 nm intermembrane 'gap'. Recent thin-section and freeze-fracture evidence has revealed significant structural variations of gap junctional structure at various stages of development and from different organisms and tissues. It is suggested that a comparative analysis of these differences may provide clues to the specific biological functions(s) of these ubiquitous organelles.


--Michael Orenstein 23:12, 4 April 2011 (EST)

References

  1. Mindaugas Rackauskas, Vaidas Neverauskas, Vytenis Arvydas Skeberdis Diversity and properties of connexin gap junction channels. Medicina (Kaunas): 2010, 46(1);1-12 PubMed 20234156
  2. P Meda, A Perrelet, L Orci Gap junctions and B-cell function. Horm. Metab. Res. Suppl.: 1980, Suppl 10;157-61 PubMed 6778805
  3. Julie Toubas, Samantha Beck, Anne-Laure Pageaud, Anne-Cecile Huby, Mouna Mael-Ainin, Jean-Claude Dussaule, Christos Chatziantoniou, Christos E Chadjichristos Alteration of connexin expression is an early signal for chronic kidney disease. Am. J. Physiol. Renal Physiol.: 2011, 301(1);F24-32 PubMed 21429966
  4. W J Larsen Structural diversity of gap junctions. A review. Tissue Cell: 1977, 9(3);373-94 PubMed 73230

--Michael Orenstein 23:16, 4 April 2011 (EST)

Gap junctions in inherited human disease - Review Article

Abstract

Gap junctions (GJ) provide direct intercellular communication. The structures underlying these cell junctions are membrane-associated channels composed of six integral membrane connexin (Cx) proteins, which can form communicating channels connecting the cytoplasms of adjacent cells. This provides coupled cells with a direct pathway for sharing ions, nutrients, or small metabolites to establish electrical coupling or balancing metabolites in various tissues. Genetic approaches have uncovered a still growing number of mutations in Cxs related to human diseases including deafness, skin disease, peripheral and central neuropathies, cataracts, or cardiovascular dysfunctions. The discovery of a growing number of inherited human disorders provides an unequivocal demonstration that gap junctional communication is crucial for diverse physiological processes.

This is a pretty general overview of diseases associated with gap junctions. As Mike said, there are alot of diseases listed- so obviously we can't go into heaps of detail with all of them. But we can definitely list a fair few and go into detail with some.

[1]

Gap junction expression is required for normal chemical synapse formation. - Current Research Article

Abstract

Electrical and chemical synapses provide two distinct modes of direct communication between neurons, and the embryonic development of the two is typically not simultaneous. Instead, in both vertebrates and invertebrates, gap junction-based electrical synapses arise before chemical synaptogenesis, and the early circuits composed of gap junction-based electrical synapses resemble those produced later by chemical synapses. This developmental sequence from electrical to chemical synapses has led to the hypothesis that, in developing neuronal circuits, electrical junctions are necessary forerunners of chemical synapses. Up to now, it has been difficult to test this hypothesis directly, but we can identify individual neurons in the leech nervous system from before the time when synapses are first forming, so we could test the hypothesis. Using RNA interference, we transiently reduced gap junction expression in individual identified neurons during the 2-4 d when chemical synapses normally form. We found that the expected chemical synapses failed to form on schedule, and they were still missing months later when the nervous system was fully mature. We conclude that the formation of gap junctions between leech neurons is a necessary step in the formation of chemical synaptic junctions, confirming the predicted relation between electrical synapses and chemical synaptogenesis.

[2]

Molecular structure of the gap junctional channel - Historic Research Article

Abstract

The proteins in various gap junctional preparations from rodent liver have been analysed by two-dimensional peptide mapping and immunoblotting. Only the protein of relative molecular mass (Mr) 16,000 (16K) is found in all gap junctional isolates, and it is unrelated to the 27K protein. The absence of the 27K protein and any of its fragments from trypsin-treated preparations suggests that this protein does not directly contribute to gap junctional structure. Peptide mapping and immunoblotting of the 16K proteins isolated from various tissues and species and of the arthropod 18K protein present in gap junctional preparations from Nephrops norvegicus show that these proteins constitute a family of related junctional proteins. A site-specific antiserum raised against the N-terminal octapeptide of the 16K protein from mouse liver cross-reacts with all 16K and 18K forms of the junctional protein so far tested, suggesting that this particular antigenic determinant is highly conserved. Immuno-localization studies show that the N-terminus is most likely located on the cytoplasmic aspect of the junction and is available to Pronase digestion.

This could be useful for structure. It's a fairly old article (1987) and only relates to gap junctions in mice, so might be worth doing some further reading on this.

[3]


References

  1. Georg Zoidl, Rolf Dermietzel Gap junctions in inherited human disease. Pflugers Arch.: 2010, 460(2);451-66 PubMed 20140684
  2. Krista L Todd, William B Kristan, Kathleen A French Gap junction expression is required for normal chemical synapse formation. J. Neurosci.: 2010, 30(45);15277-85 PubMed 21068332
  3. M E Finbow, T E Buultjens, S John, E Kam, L Meagher, J D Pitts Molecular structure of the gap junctional channel. Ciba Found. Symp.: 1987, 125;92-107 PubMed 3030674

--Elizabeth Blanchard 21:10, 5 April 2011 (EST)


Gap junctions in inherited human disease

Abstract

Gap junctions (GJ) provide direct intercellular communication. The structures underlying these cell junctions are membrane-associated channels composed of six integral membrane connexin (Cx) proteins, which can form communicating channels connecting the cytoplasms of adjacent cells. This provides coupled cells with a direct pathway for sharing ions, nutrients, or small metabolites to establish electrical coupling or balancing metabolites in various tissues. Genetic approaches have uncovered a still growing number of mutations in Cxs related to human diseases including deafness, skin disease, peripheral and central neuropathies, cataracts, or cardiovascular dysfunctions. The discovery of a growing number of inherited human disorders provides an unequivocal demonstration that gap junctional communication is crucial for diverse physiological processes.

There is a good/brief overview of the structure/function of connexins at the beginning of the article, as well as details on diseases related to gap jcts.


[1]

References

  1. Georg Zoidl, Rolf Dermietzel Gap junctions in inherited human disease. Pflugers Arch.: 2010, 460(2);451-66 PubMed 20140684

--Elizabeth Blanchard 22:53, 13 April 2011 (EST)