Talk:2011 Group 2 Project
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)
- 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.
- I see many groups now have subsection titles for their projects.
- 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.
- 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#]].
- 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:
- A Review Article
- A Historic Research Article
- A Current Research Article
No two students should add the same paper and there should be a link to the original article.
--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
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
(2) Discovery/History - who discovered gap junctions
(3) Structure - what they look like/how they are formed
(4) Function(importance) - their job
(5) Location - where they are found/why
(6) Comparison - briefly explain how our junction is different from others
(7) Diease - possibly something to do with dieases associated with abnormalties of the junction
(8) Research - current research of gap junctions/new research and discoveries
--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.
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.
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.
- <pubmed>15109565 </pubmed>
--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.
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. 
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. firstname.lastname@example.org
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. 
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)
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.
--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  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  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  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.
--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  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  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  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.
- <pubmed> 20664797 </pubmed>
--z3253348 19:41, 4 April 2011 (EST)
Diversity and properties of connexin gap junction channels. (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. (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. (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.
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)
- <pubmed> 20234156 </pubmed>
- <pubmed> 6778805 </pubmed>
- <pubmed> 21429966 </pubmed>
- <pubmed> 73230 </pubmed>
--Michael Orenstein 23:16, 4 April 2011 (EST)
Gap junctions in inherited human disease - Review Article
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.