2011 Group 5 Project

From CellBiology
Residual membrane tethers in disrupted Adherens Junctions

Adherens Junctions

Introduction

What is a cell junction?

Cells are the building blocks of life. Living organisms are made up of millions of cells making up tissues, organs and systems. In vertebrates there are several types of tissues including nerve, muscle, blood, lymphoid, epithelial and connective tissues. Cell junctions are specialized regions of connection between two cells or between a cell and the extracellular matrix. They are particularly important in epithelial tissue which is arranged from tightly bound cells held together by cell junctions. [1]The adhesion of cell to cell junctions binding the cytoskeletons of two cells allows cells of an epithelial sheet to function as a coordinated tissue.[2]

Epithelial sheet of the exocervix - cell junctions between cells allow them to function as a coordinated tissue

There are several types of cell junctions including tight junctions, desmosomes, hemidesmosomes, tunneling nanotubes, gap junctions and neuromuscular junctions but on this page we will focus on the adherens junction which functions to mechanically attach two cells together by linking the actin filaments of two cells together.


These 7 types of junctions can be classified into three classes based on their kind of function:

  1. Occluding junctions - seals cells together to prevent movement of molecules over the epithelial sheet.
  2. Anchoring junctions - attaches cells to cells or cells to the extracellular matrix.
  3. Communicating junctions - allows passage of chemical or electrical signals between cells.[3]


What is an Adherens Junction?

Summary of cell junction types showing the adhesion belt below the tight junction
Adherens junctions are anchoring junctions, binding bundles of actin filaments between adjacent cells via the key protein cadherin, supported by other proteins called catenins, namely aplha and beta catenin. They are found mostly in tissues under severe mechanical stress such as the heart, muscle and epidermis.[4] In epithelia the adjacent adherens cell junctions form a continuous adhesion belt lying at the apical end of the cells below the tight junctions. Contractions of the actin bundles in adjacent cells leads to the apical end of the cell shrinking, altering the shape of the epithelial sheet into rolled structures. A function of this unique ability of adherens junctions is evident in the development of the neural tube and eye lens in embryonic development.[5]

Research on these vital junctions can be found as far back as 1839 and we will explore the progress of our understanding of these junctions from that time until the present day. The structure and function of these junctions will be explained in detail as well as the importance and regulation and diseases associated with them. Lastly the current research being conducted into the area of adherens junctions will be explored.

History

1839- Theodor Schwann and Matthias Schleiden hypothesis that “animal cells might fuse at specific points via cytoplasmic bridges”.[6]


1944- First electron micrograph of a cell by Keith Porter, Albert Claude and Ernest Fullman, in 1944, at the Rockefeller University (New York). [7]


1961- Farquhar and Palade define three of the four cell to cell junction , one of them being adherens junctions. Their location below tight junctions is also identified.[8]


1977– Cadherins, the adhesion molecule are first identified in adherens junctions by Masatoshi Takeichi.[9]


1982- “N-cadherin was first identified in 1982 (Grunwald et al., 1982) as a 130 kD molecule in the chick neural retina that was protected by calcium from proteolysis”.[10]

Shoichiro Tsukita


1989- Tsukita and Tsukita are the first to isolate intact adherens junctions from preparation of rat liver hepatocytes.[11]


1992- Tsukita et al suggest that alpha catenin links the cadherin complex to the cytoskeleton.[12]


2000- “N-cadherin can engage also in heterotypic homophilic and heterophilic interactions with other caherins (Shan et al, 2000)”[13]


2008- In 2008 Avalon Pharmaceuticals identified a compound for clinical development, named AVN316, that could potentially inhibits the beta-catenin pathway in a variety of model systems.[14]


2011- N-cadherin identified as an immunohistochemical marker strongly associated with hepatitis virus infection.[15]

Structure

Adherens Junction Diagram.jpg


Adherens junctions are based on Cadherins

Adherens junctions are cell to cell junctions that connect bundles of actin filaments between cells. These specialized junctions are formed from proteins called cadherins.[16] Cadherins are cell adhesion molecules that mediate calcium dependent junctions.
Homophillic binding of cadherin dimers
There are classical and non-classical types of cadherin protein molecules, together making up what is called the cadherin superfamily of proteins. Classical cadherins including E-cadherin, N-cadherin and P-cadherin are associated with adherens junctions whereas non-classical cadherins including Desmocollin and Desmoglein are associated with desmosomes. Studies have shown that cadherin binding is strictly homophilic binding, meaning only two of the same types of cadherin protein molecules may bind together. This was proved by mixing cells expressing different cadherin types, resulting in segregation based on their types. An interesting example of this occurs during neural tube formation during embryo development. The separation of the ectoderm layer from the forming neural tube can be attributed to the expressions of two different cadherins, E- and N-cadherin in the separate layers, meaning these two tissues form independent of each other. [17]


Linked cadherin molecules
Cadherins are glycoprotein chains approximately 700-750 amino acid units long which are folded into polypeptide chain repeats. These repeats are alternated with calcium ions which function to hold the chain together into a stiff structure, strong enough to link with other cadherin molecules in adjacent cells forming a strong cell adhesion junction.[16]This means adherens junctions depend on extracellular calcium to function properly in cell adhesion.

Catenins link Cadherins

The transmembrane cadherin protein molecules are connected to intracellular actin filaments in cells via anchor proteins alpha and beta catenin.
Epithelial sheet stained for beta catenin at cell junctions
These extra linker proteins are key in the structure of adherens junctions as cadherin molecules are not strong enough to bind the actin cytoskeletons of two cells by themselves.[18]

An adhesion junction cannot be formed without the formation of a cadherin and beta catenin complex as the first step. The 781 amino acid beta catenin binds strongly to the cadherin by a process of phosphorylation and it has been shown that mutations at these phosphorylation sites on the proteins can effectively reduce cell adhesion.[19] It was originally thought that alpha catenin acted as the bridge holding the cadherin-beta catenin complex to the actin filaments. Further research has suggested that alpha catenin doesn't join these proteins together but actually acts as a regulatory protein, regulating filamentous actin dynamics.[20] Alpha catenin molecules function to bundle actin fibers into stronger filaments to support the junction stability.[21]


Animated Video

VIDEO:Adherens junction structure animation This three dimensional animated video shows how two cells with like cadherin molecules bind together, gathering more cells forming a stable epithelial sheet. It also depicts a key function of these junctions detailed below of the separation of the neural tube from the ectodermal layer during embryo development.

Function

Adherens junctions have a variety of functions, they particularly play a vital role in cell to cell adhesion and cell to matrix adhesion. Furthermore adherens junctions are or have been hypothesised to be important factors in the proper function of tissue homeostasis, permeability, cell signalling, transportation, embryogenesis and neural tube formation. So far there is knowledge that adherens junctions play a vital role in many biological processes and what the outcomes would be if there is a dysfunction with this adhesion type, such as gene deletion or mutation. However the exact molecular mechanism in which this junctions functions is still an area of uncertainty.

A schematic of VE-cadherin-mediated adherens junctions in epithelial cells.


The ability of adherens junction to maintain cell to cell adhesion allows for the maintenance of the epithelial barrier, which acts to protect us from the outside world, as well as preventing unnecessary water loss. An excellent example the crucial roles adherens junctions play in epithelial adhesion is the experiment where the alpha-catenin is specifically deleted in mice. The results of this study showed detachment of the epidermis, associated with the loss of intercellular adhesion and adherens junctions [22].


Adherens junction have role in the connectivity of endothelial cells and the homeostasis of the blood vessels by “controlling the movement of solutes between the blood stream and the sourrounding tissue”[23] and the infiltration of leucocytes between blood and tissue in particular at sites of inflammation. One of the theories on the molecular basis, on the maintenance of vascular permeability and homeostasis is that the actomyosin that is anchored to the adherens junctions contract to allow for opening up of the adherens junction.[24].


Furthermore adherens junction have been seen playing a vital role in embryogenesis as they regulate epidermal assembly and cell polarity. During embryogenesis if catenin molecules are absent or mutated, the embryoblast will lose its adhesion and fail to continue its development[25] In addition the N-cadherin molecules function in the development of an embryo were it is regulated as necessary for the migration of neural crest cells and the closure of the neural tube.[26]


Video A schematic of VE-cadherin-mediated adherens junctions. Adherens junctions are formed by the calcium-dependent homophilic binding between extracellular amino-terminal domains of VE-cadherin molecules from the adjacent cells. adherens junctions

Importance and Regulation

Remodeling of Adherens Junctions


The Adherens Junction is an essential feature in mammals; it provides the protection to our skin (epidermis). On top of that the ability to contract the epithelial or endothelial tissue make this junction is an important factor when it comes to embryonic development [5]. It gives rise to the structure of neural tube and lens of the eye. The Adherns Junction also regulates the vescular permeability of which their impaired function can lead to several pathological conditions. Examples of these pathological conditions are inflammation, sepsis, ischemia and diabetes. The ischemic tissue injury can also cause different sorts of diseases such as stroke or myocardial infarction. [27]

Adherens Junction.JPG

The important feature in Adhrens junction is the Ca2+ dependent Cadherin intermembrane protein, the catenin cytoplasm protein and the actin filaments. The regulation of this Junction can be at the level of intercellular or extracellular level. The regulation can occur at the site of the E-cadherin protein complex formation, the level of cadherin/catenin (which binds to actin filament) binding site or the cadherin/cadherin homophilic binding site.


Concentration of Ca2+ is important in the extracellular space. The calcium binds the Cadhedrin proteins together in order for the Adhesion Junction to be formed. With out this the cell-cell homophilic binding of adhesion cells are not possible. Therefore the level of Ca2+ can be a good regulator for the Adherens Junction. The ranges of extra cellular signals that can regulate the Adherens Junction at this site are; growth factors, the peptide hormones and …etc. [28].


The Rho family of GTPase are another essential regulator for the Junction. This occurs at the site of cytoplasm tail of E-cadherin interacting with the actin cytoskeleton via catenin which binds the actin and cadhedrin together. The Rho family act as the the ‘molecular switch’ which allows the cycle inbetween GTP-bound stace and GDP-bound state, allowing regulation of both the assembly and disassembly of adherens junction by gathering of E-cadherin, b-catenin and actin at the site of cell-cell contacts. [29] Rho Family GTPases and Cellular Transformation

743px-Protein IQGAP1 PDB 1x0h.png


Also the IQGAP1 seem to be a important regulator co-working with Rho family GTPases, to regulate cell adhesion, polarization and migration. When it is over expressed, it interacts with β-catenin which dissociate of α-catenin from the cadherin-catenin complex, hense reducing the E-cadherin based cell-cell adhesion. Vice versa, the activated Rac1 and Cdc42 positively regulate E-cadherin-mediated cell-cell adhesion by inhibiting the interaction of IQGAP1 with β- catenin [30]. It not only down regulate at Adherens Junction but lead to estabilishment of polarised cell morphology and directional cell migration.


There are more factors that regulate the Adherens junctions. However, there are more areas to be researched. The importance of this junction if quite clear and if this can be controlled correctly, it can be a huge step in medical fields.

Abnormalities of Adherens Junctions

Listeria monocytogenes

Listeria monocytogenes - Meningitis, Encephalitis, Septicemia, Endocarditis, Abortion, Abscesses, Listeriosis

Listeria monocytogenes, an intracellular bacterium, is the causative agent of listeriosis. It is one of the most virulent foodborne pathogens, with 20 to 30 percent of clinical infections resulting in death. It causes invasive disease by crossing the intestinal epithelial barrier. This process depends on the interaction between the bacterial surface protein Internalin A and the host protein E-cadherin. Biochemical studies have shown that both tight junction proteins and adherens junction proteins are degraded in apoptotic cells, which may facilitate their detachment from neighboring cells. By detaching, these junctions are no longer able to function and encounter apoptosis. [31]


Polycystic Kidney Disease

Polycystic kidney disease is a disease of the nephron, characterised by the formation of multiple renal tubular cysts, leading to endstage renal failure. Autosomal Dominant Polycystic Kidney Disease is caused by mutations in the genes encoding polycystin-1 and/or polycystin-2, but results in epithelial cells with disrupted adherens junctions and compromised beta-catenin signaling pathways. More information can be found Autosomal dominant polycystic kidney disease: the last 3 yearsAutosomal dominant PKD


Ulcerative Colitis and colorectal carcinomas
Ulcerative Colitis

CD97 is a protein that in humans is encoded by the CD97 gene and induces specific signaling that results in a decrease of proteolytic digestion of β-catenin. It is a major factor in stabilisation within adherens junctions and thus causes breakdowns within the structure of the junction itself. [32] This occurs in both Ulcerative Colitis and Colorectal carcinomas as both are located in the colon. [33]


Dengue Fever

Increased vascular permeability is a main feature in severe dengue virus infections as well as the dysfunction of endothelial cells to contributing to the pathogenesis of dengue hemorrhagic fever/dengue shock syndrome. Small signaling GPTase enzymes (that regulate intracellular Actin dynamics) are significant elements of endothelial barrier function regulation and has been implicated in the regulation of actin remodeling and intercellular junction formation. In the absence of vasoactive stimuli, dominant negative Rac1 (a dominant enzyme in this GTPase family) increases endothelial permeability and affects adherens and tight junctions. [34]


Transmission electron micrograph of hantavirus

HantaViruses

Recent disease research by Gorbunova E., Gavrilovskaya I. and Mackow, R has shown that the Anders and Hantaan Viruses (pathogenic hanatviruses) disrupt fluid barrier properties of endothelial cell adherens junctions by enhancing the specific cadherin pathway responses which increase paracellular permeability. For more information please follow the link... Pathogenic Hantaviruses Andes Virus and Hantaan Virus Induce Adherens Junction Disassembly by Directing Vascular Endothelial Cadherin Internalization in Human Endothelial Cells

Current Research

Placenta Growth Factor-1 Exerts Time-Dependent Stabilization of Adherens Junctions Following VEGF-Induced Vascular Permeability 2011

Cai et al. discuss the role of the placenta growth factor (PIGF) and its isoforms 1 and 2 in regulating vascular permeability associated with the rapid localisation of specific cadherin to the plasma membrane, specifically in adherens Junctions. The time period in which this growth factor exerts its effect on the stability of the junction highlights its ability to be used as an endogenous anti-permibility factor whose effectiveness is limited to a precise time point following vascular injury. [35]
FPEX Research by the Idaho National Laboratory


Adherens junctions connect stress fibres between adjacent endothelial cells 2010

Endothelial cell-cell junctions can attach to the ends of stress fibres instead of to cortical F-actin, forming structures that are named discontinuous adherens junctions. These junctions are highly dynamic and are increased in response to tumour necrosis factor (TNF)-α, correlating with the appearance of stress fibres. Theses fibres from neighbouring cells are physically connected through discontinuous Adherens Junctions, and that stress fibres can be stabilized by Adherens Junction-associated multi-protein complexes distinct from focal adhesions.[36]


PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherins 2010

The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified by Pulimeno et al. as a protein linking the E-cadherin- complex to the microtubule cytoskeleton. They were able to characterise. The proteins function, expression and localisation whist also labelling the junctions regions within cultured kidney cells. Specifically they established that definitively establishes that PLEKHA7 is localized at the adherens junctions in colonic epithelial cells.[37]


Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions 2010

The adhesion G-protein-coupled receptor CD97 is present in normal colonic enterocytes but overexpressed in colorectal carcinoma. Noticing this, Becker et al. researched showed that this CD97 antigen increases the structural integrity of enterocytic adherens junctions by increasing and stabilizing junctional β-catenin, and as such, the heavily cadherin dependent Adherens junctions. Thereby, this paper explains how CD97 regulates intestinal epithelial strength and attenuating experimental colitis.[38]


A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis 2009

Invasion through the extracellular matrix is important for wound healing, immunological responses and metastasis.Through use of Invasion-based motility assays, Finlayson et al were able to identify an antisnese related protein whose family member, MARCKS related protein (MPR), was involved in tumor growth, invasion and metastesis in multiple human cancers. They were also able to identify an increased in the number of E-cadherin, β-catenin and adenomatous polyposis coli (APC) protein at sites of cell-cell contact in cells with MRP knockdown suggesting formation of adherens junctions. As a whole their data suggest that reducing MRP expression promotes formation of adherens junctions, allowing collective cell migration, but interferes with oncogenic β-catenin signaling and tumorigenesis.[39]

Microscopy by the Idaho National Laboratory

Future Research

From the Current Research articles that has been reviewed, it has highlighted the need for future research within their specific areas on Adherens Junctions. We can see here that the following questions need to be explored...


  • A more complete understanding of how temporal expression of pro- and anti-angiogenic agents function in vivo to regulate vascular permeability, particularly in adherens junctions. This future research will be essential in order to maximise the therapeutic potential of anti-angiogenic therapies and therapies that directly treat increased vascular permeability. [40]


  • Experimentation into the proposal that the linkage of stress fibres between neighbouring cells via discontinuous adherens junctions contributes to increase stress resistance and to regulate the whole endothelial monolayer response to inflammation. With this knowledge, our abilities to be able to control the inflammation process will be invaluable. [41]


  • By using the cellular and animal model systems, discovering whether adherens junction stabilisation through PLEKHA7-dependent microtubule anchoring is important in cancer development and progression. The specific antibodies against PLEKHA7 will be a valuable tool for this purpose, and could also be useful in the histological typing and diagnosis of tumors. [42]


  • Identifying the unknown function of the adhesion G-protein-coupled receptor of CD97, in relation to tumor and colitis-associated models. By identifying the function, it will enable control over the over-expression of CD97 and thus decrease colitis sensitivity. [43]


  • By exploring the reduction of MRP (MARCKS related protein) that it would promote metastasis without interfering with tumorigenesis in such instances. Using cell lines that are not dependent on the β-catenin pathway (found in adherens junctions) for transformation may allow modeling the role of MRP knockdown in cancer invasion and metastasis, in vivo. [44]

Other types of Cell Junctions

Adherens junctions are anchoring junctions, similar to desmosomes and hemidesmosoms. Adherens junctions and desmosomes anchor cells to cells via the protein cadherin, whereas hemidesmosomes anchor cells to the extracellular matrix and are formed from integrin proteins. However, there are four other cell junctions which have very different functions to adherens junctions and these contrasts will be explained below:


Types of Cell Junctions
Junction Type of junction Key Proteins Function Diagram
Tight Junction OCCLUDING junction: Seals cells together to prevent leakage of molecules between them and through the epithelial sheet.[45] Claudins and occludins[5] Tight junctions are the junctions between cells that form an epithelial sheet throughout the body. They seal the adjacent cells together in a band just below the apical surface, the surface that is exposed to the lumen. They are important in preventing molecules leaking between the cells, providing control of passage of materials through the epithelial sheet as the cells must diffuse through the cells themselves to pass through.[46] Tight junction.png
Gap Junction COMMUNICATING junction: Mediates the passage of chemical or electrical signals between cells.[45] Connexons[5] Gap junctions form channels between cells approximately 1.5-2 nanometers in diameter for the passage of ions and small molecules. These function to regulate the membrane potential between cells and allow electrical impulses to pass between cells. Examples of this includes electrical impulses passing between cardiac muscle cells creating the heart beat. Also gap junctions provide the contractions of the smooth muscle cells of the uterus during birth.[47][48] Gap junction cartoon1.jpg
Desmosomes ANCHORING junction: mechanically attaches cells to their neighbors.[45] Cadherins [5] These function to attach two epithelial cells together by their intermediate filaments, in particular holding the stratified epithelium of the epidermis together. These are similar to adherens junctions as they anchor two cells together by cadherin proteins which bind in a strong homophilic way.[49] Desmosome image.png
Tunneling Nanotubes COMMUNICATING junction: Mediates the passage of chemical or electrical signals between cells over a longer distance.[50] Motor protein myosin Va[51] Tunneling nanotubes form thin membrane channels between cells over a longer distance than gap junctions, up to several cell diameters in distance[52], and are also wider in diameter, approximately 50-200 nanometers wide.[53] They not only allow the passage of proteins between cells but also of organelles. Due to their sensitive structure they have only recently been discovered and studies on them have been limited. Nanotube.jpg
Hemidesmosome ANCHORING junction: Mechanically attaches cells to its basal lamina.[45] Integrin proteins[5] With the appearance of half a desmosome, hemidesmosomes anchor cells to the basal lamina. Even though they have a similar appearance, hemidesmosomes bind using integrin proteins and not the cadherins that desmosomes use. They play important roles in the basal cells of stratified epithelia, but particularly in epidermal to dermal adhesion of the skin. Integrin proteins in the basal plasma membrane of the epithelial cells bind to laminin, an extracellular matrix protein in the basal lamina.[5] Tracheal hemidesmosomes.JPEG
Neuromuscular Junction COMMUNICATING junction: Mediates the passage of chemical or electrical signals between cells. Acetylcholine receptor[54] associated with rapsyn[55] and cortactin proteins[56] A neuromuscular junction is the synapse of the axon terminal of a motor neuron with the end plate of a muscle fibre. The signal transmission from the the neuron to the muscle cell occurs due to the release of the chemical acetylcholine which binds to a protein receiver on the muscle called the acetylcholine receptor. Neuromuscular junctions are essential for muscle function in vertebrates.[57]
Detailed view of a neuromuscular junction:
1. Presynaptic terminal
2. Sarcolemma
3. Synaptic vesicle
4. Nicotinic acetylcholine receptor
5. Mitochondrion

Glossary

A

Actin Cytoskeletal 43 kD protein forming the backbone of the cytoplasmic microfilament system and the thin filament system of muscle sacomeres. In humans, there are distinct muscle (4 alpha-skeletal, alpha-cardiac, alpha-smooth, gamma-smooth) and non-muscle (2 cytoskeletal beta-, gamma-) actin isoforms. Exists as globular actin monomer (G-actin) and microfilament polymer (F-actin).

Actomyosin Actomyosin is a protein complex in muscle fibers which is composed of myosin and actin. It shortens when stimulated and causes muscle contractions.

Adenomatous Polyposis Coli Protein A negative regulator of beta-catenin signaling. These gene is associated with familial adenomatous polyposis (FAP), an inherited disorder characterized by the development of myriad polyps in the colon. The gene is located on chromosome 5. [58]

Amino acid One of the 20 building blocks of protein. The sequence of amino acids in a protein and, hence, the function of that protein are determined by the genetic code in the DNA. Amino acids are molecules that (in technical terms) contain a basic amino (NH2) group, an acidic carboxyl (COOH) group and a side chain attached to an alpha carbon atom. [59]

Anchoring Junctions A junction that connects the cytoskeleton (actin filaments) of a cell to the extracellular matrix or to the cytoskeleton of surrounding cells.

Angiogenesis The formation of new blood vessels in the body. There are two types of drug therapies based on controling blood vessel growth, Pro- and angiogenic therapies.

Antisnese Having a sequence of nucleotides complementary to a coding sequence, which may be either that of the strand of a DNA double helix that undergoes transcription, or that of a messenger RNA molecule. [60]

C

Cadherins Calcium-dependent cell-adhesion molecules.[61]

Catenin Any of a family of 80-102-kilodalton proteins that are thought to have a major role in regulation of cell-to-cell adhesion, which is related to their interaction with E-cadherin and the actin cytoskeleton.

CD97 Primary antibodies; Rabbit polyclonal to CD97 Immunogen: A portion of amino acids 220-270 of human CD97

Cell Signaling Is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. [62]

Cytoskeleton Set of 3 filament systems intermediate filaments, actin filaments, and microtubules. Eukaryotic cells have a cytoplasmic and a nuclear cytoskeleton with different organisations and filaments.

E

Embryoblast Any of the germinal disk cells of the inner cell mass in the blastocyst that form the embryo.

Embryogenesis The development and growth of an embryo, especially the period from the second week through the eighth week following conception

Enterocytes A cell that lines the intestinal wall.

Epithelial Tissue membranous tissue covering internal organs and other internal surfaces of the body.

Epidermis The outermost layer of the surface epithelium.

Extracellular Matrix An insoluble protein scaffold on which cells reside. The extracellular matrix provides the structure and attachment sites, and signals through cell surface receptors. Epithelial cells, endothelial cells and adipocytes rest on a specialized extracellular matrix called the basement membrane.

F

F-actin Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells (the only known exception being nematode sperm) where it may be present at concentrations of over 100 μM.

G

Glycoprotein A molecule that consists of a carbohydrate plus a protein.[63]

H

Hantavirus A type of virus carried by rodents causing severe respiratory infections in humans and, in some cases, hemorrhaging, kidney disease, and death.

Homophilic Binding A process that is involved in cell adhesion, also called cell-junction. Homophilic binding is a binding between two identical components of the cell junction.

I

Integrin (protein) A heterodimeric transmembrane receptor protein of animal cells that binds to components of the extracellular matrix on the outside of a cell and to the cytoskeleton on the inside of the cell, functionally connecting the cell interior to its exterior.

Intermembrane Protein Represent a class of proteins located in the lipid bilayer of the cell membrane which function as ion channels.

U

Ulcerative Colitis a serious chronic inflammatory disease of the large intestine and rectum characterized by recurrent episodes of abdominal pain and fever and chills and profuse diarrhea.

References

  1. Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002.
  2. Mirna Perez-Moreno, Colin Jamora, Elaine Fuchs Sticky business: orchestrating cellular signals at adherens junctions. Cell: 2003, 112(4);535-48 PubMed 12600316
  3. Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002.
  4. Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Bruce Alberts (2010). Essential Cell Biology.(3rd Ed). New York: Garland Science, Taylor and Francis Group.
  6. William A. Wells, March 28th 2005, Defining junctional complexes. http://jcb.rupress.org/content/168/7/989.full
  7. Cathárine C. Calkins1 and Shannon V. Setzer1, 2007, Spotting Desmosomes: The First 100 Years. http://www.nature.com/milestones/skinbio1/full/milestone1.html
  8. William A. Wells, March 28th 2005, Defining junctional complexes. http://jcb.rupress.org/content/168/7/989.full
  9. Kendall Powell, August 15th 2005, The sticky business of discovering cadherins. http://jcb.rupress.org/content/170/4/514.full
  10. LARA D.M. DERYCKE and MARC E. BRACKE, N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling.
  11. Alan.R. Parrish, Jeffery. M. Catania, Jason Orozco and A. Jay. Gandolfi, 1999, Chemically Induced Oxidative Stress Disrupts the E-cadherins/catenin Cell Adhesion Complex. http://toxsci.oxfordjournals.org/content/51/1/80.full.pdf
  12. Alan.R. Parrish, Jeffery. M. Catania, Jason Orozco and A. Jay. Gandolfi, 1999, Chemically Induced Oxidative Stress Disrupts the E-cadherins/catenin Cell Adhesion Complex. http://toxsci.oxfordjournals.org/content/51/1/80.full.pdf
  13. http://www.copewithcytokines.org/cope.cgi?key=N-cadherin
  14. http://www.avalonpharma.com/
  15. Tsan-Hua Yu, Ray-Hwang Yuan, Yu-Ling Chen, Wan-Ching Yang, Hey-Chi Hsu and Yung-Ming Jeng, 2011, Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression.
  16. 16.0 16.1 Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002.
  17. Lawrence Shapiro, William I Weis Structure and biochemistry of cadherins and catenins. Cold Spring Harb Perspect Biol: 2009, 1(3);a003053 PubMed 20066110
  18. Jacqueline M Benjamin, Adam V Kwiatkowski, Changsong Yang, Farida Korobova, Sabine Pokutta, Tatyana Svitkina, William I Weis, W James Nelson AlphaE-catenin regulates actin dynamics independently of cadherin-mediated cell-cell adhesion. J. Cell Biol.: 2010, 189(2);339-52 PubMed 20404114
  19. Lawrence Shapiro, William I Weis Structure and biochemistry of cadherins and catenins. Cold Spring Harb Perspect Biol: 2009, 1(3);a003053 PubMed 20066110
  20. Saumendra Bajpai, Yunfeng Feng, Ranjini Krishnamurthy, Gregory D Longmore, Denis Wirtz Loss of alpha-catenin decreases the strength of single E-cadherin bonds between human cancer cells. J. Biol. Chem.: 2009, 284(27);18252-9 PubMed 19458087
  21. Jacqueline M Benjamin, Adam V Kwiatkowski, Changsong Yang, Farida Korobova, Sabine Pokutta, Tatyana Svitkina, William I Weis, W James Nelson AlphaE-catenin regulates actin dynamics independently of cadherin-mediated cell-cell adhesion. J. Cell Biol.: 2010, 189(2);339-52 PubMed 20404114
  22. Carien M. Niessen1,2, Tight Junctions/Adherens Junctions: Basic Structure and Function, 1Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany and 2Department of Dermatology, University of Cologne, Cologne, Germany. http://www.nature.com/jid/journal/v127/n11/full/5700865a.html
  23. Maria Grazia Lampugnani, 2010, Endothelial adherens junctions and the actin cytoskeleton: an 'infinity net'?
  24. Elisabetta Dejana, Fabrizio Orsenigo and Maria Grazia Lampugnani, 2008, The role of adherens junctions and VE-cadherin in the control of vascular permeability
  25. Rachel T. Cox, Catherine Kirkpatrick, and Mark Peifer, 1996, Armadillo Is Required for Adherens Junction Assembly, Cell Polarity, and Morphogenesis during Drosophila Embryogenesis.
  26. http://www.dnatube.com/video/169/Cadherins-Structure-and-Function-Part-III--Adherens-Junctions-and-Tissue-Morphogenesis-
  27. Elisabetta Dejana, Fabrizio Orsenigo, Maria Grazia Lampugnani The role of adherens junctions and VE-cadherin in the control of vascular permeability. J. Cell. Sci.: 2008, 121(Pt 13);2115-22 PubMed 18565824
  28. A S Yap, W M Brieher, B M Gumbiner Molecular and functional analysis of cadherin-based adherens junctions. Annu. Rev. Cell Dev. Biol.: 1997, 13;119-46 PubMed 9442870
  29. Mirna Perez-Moreno, Colin Jamora, Elaine Fuchs Sticky business: orchestrating cellular signals at adherens junctions. Cell: 2003, 112(4);535-48 PubMed 12600316
  30. Jun Noritake, Takashi Watanabe, Kazumasa Sato, Shujie Wang, Kozo Kaibuchi IQGAP1: a key regulator of adhesion and migration. J. Cell. Sci.: 2005, 118(Pt 10);2085-92 PubMed 15890984
  31. http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0020003 Pentecost M, Otto G, Theriot JA, Amieva MR (2006) Listeria monocytogenes Invades the Epithelial Junctions at Sites of Cell Extrusion. PLoS Pathog 2(1): e3. doi:10.1371/journal.ppat.0020003
  32. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008507 Becker S, Wandel E, Wobus M, Schneider R, Amasheh S, et al. (2010) Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions. PLoS ONE 5(1): e8507. doi:10.1371/journal.pone.000850
  33. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0020230 Wijmenga C (2005) Expressing the Differences between Crohn Disease and Ulcerative Colitis. PLoS Med 2(8): e230. doi:10.1371/journal.pmed.0020230
  34. http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000809 Wang J-L, Zhang J-L, Chen W, Xu X-F, Gao N, et al. (2010) Roles of Small GTPase Rac1 in the Regulation of Actin Cytoskeleton during Dengue Virus Infection. PLoS Negl Trop Dis 4(8): e809. doi:10.1371/journal.pntd.0000809
  35. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018076 Cai J, Wu L, Qi X, Shaw L, Li Calzi S, et al. (2011) Placenta Growth Factor-1 Exerts Time-Dependent Stabilization of Adherens Junctions Following VEGF-Induced Vascular Permeability. PLoS ONE 6(3): e18076. doi:10.1371/journal.pone.0018076
  36. http://www.biomedcentral.com/1741-7007/8/11
  37. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012207 Pulimeno P, Bauer C, Stutz J, Citi S (2010) PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin. PLoS ONE 5(8): e12207. doi:10.1371/journal.pone.0012207
  38. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008507 Becker S, Wandel E, Wobus M, Schneider R, Amasheh S, et al. (2010) Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions. PLoS ONE 5(1): e8507. doi:10.1371/journal.pone.000850
  39. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007833 Finlayson AE, Freeman KW (2009) A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis. PLoS ONE 4(11): e7833. doi:10.1371/journal.pone.0007833
  40. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018076 Cai J, Wu L, Qi X, Shaw L, Li Calzi S, et al. (2011) Placenta Growth Factor-1 Exerts Time-Dependent Stabilization of Adherens Junctions Following VEGF-Induced Vascular Permeability. PLoS ONE 6(3): e18076. doi:10.1371/journal.pone.0018076
  41. http://www.biomedcentral.com/1741-7007/8/11
  42. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012207 Pulimeno P, Bauer C, Stutz J, Citi S (2010) PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin. PLoS ONE 5(8): e12207. doi:10.1371/journal.pone.0012207
  43. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008507 Becker S, Wandel E, Wobus M, Schneider R, Amasheh S, et al. (2010) Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions. PLoS ONE 5(1): e8507. doi:10.1371/journal.pone.000850
  44. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007833 Finlayson AE, Freeman KW (2009) A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis. PLoS ONE 4(11): e7833. doi:10.1371/journal.pone.0007833
  45. 45.0 45.1 45.2 45.3 http://www.ncbi.nlm.nih.gov/books/NBK26857/table/A3473/
  46. Caitlin D Blaskewicz, Jeffrey Pudney, Deborah J Anderson Structure and function of intercellular junctions in human cervical and vaginal mucosal epithelia. Biol. Reprod.: 2011, 85(1);97-104 PubMed 21471299
  47. W Howard Evans, Patricia E M Martin Gap junctions: structure and function (Review). Mol. Membr. Biol.: 2002, 19(2);121-36 PubMed 12126230
  48. T H Steinberg Gap junction function: the messenger and the message. Am. J. Pathol.: 1998, 152(4);851-4 PubMed 9546343
  49. Gethin R Owen, David L Stokes Exploring the Nature of Desmosomal Cadherin Associations in 3D. Dermatol Res Pract: 2010, 2010;930401 PubMed 20672011
  50. http://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=Cell_Junctions
  51. Kimberly L Gallagher, Philip N Benfey Not just another hole in the wall: understanding intercellular protein trafficking. Genes Dev.: 2005, 19(2);189-95 PubMed 15655108
  52. http://biology.ucsd.edu/classes/bisp194.SP08/Gerdes%202007%20FEBS%20rev.pdf
  53. http://www.authorstream.com/Presentation/Aisha-110958-tunnelling-nanotube-tnt-nanotubes-cells-tunneling-science-technology-ppt-powerpoint/
  54. S Hirose, W R Vieth Transport of acetylcholine in a membrane. Laminate model of the neuromuscular junction. Appl. Biochem. Biotechnol.: 1984, 9(1);81-93 PubMed 6476821
  55. C Fuhrer, M Gautam, J E Sugiyama, Z W Hall Roles of rapsyn and agrin in interaction of postsynaptic proteins with acetylcholine receptors. J. Neurosci.: 1999, 19(15);6405-16 PubMed 10414969
  56. Raghavan Madhavan, Zhuolin L Gong, Jin Jin Ma, Ariel W S Chan, H Benjamin Peng The function of cortactin in the clustering of acetylcholine receptors at the vertebrate neuromuscular junction. PLoS ONE: 2009, 4(12);e8478 PubMed 20041195
  57. S Hirose, W R Vieth Transport of acetylcholine in a membrane. Laminate model of the neuromuscular junction. Appl. Biochem. Biotechnol.: 1984, 9(1);81-93 PubMed 6476821
  58. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007833 Finlayson AE, Freeman KW (2009) A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis. PLoS ONE 4(11): e7833. doi:10.1371/journal.pone.0007833
  59. Medicine Net (2011). http://www.medterms.com/script/main/art.asp?articlekey=2222
  60. MEdicine Net (20011), http://www.medterms.com/script/main/art.asp?articlekey=20468
  61. The Free Dictionary (2011). http://medical-dictionary.thefreedictionary.com/cadherins
  62. http://en.wikipedia.org/wiki/Cell_signaling
  63. Medicine Net (2011).http://www.medterms.com/script/main/art.asp?articlekey=16842


Coordinator Comment to all Groups

I will add a general comment that will be the same to all groups under this heading.

Referencing Extension Problem

--Mark Hill 13:16, 3 May 2011 (EST) As mentioned in the lecture, I am aware of the referencing extension problem on your project pages. I have the following temporary solution, of removing the extension, so that groups can continue to add content to their project pages. I am also giving everyone a 1 week extension before the peer assessment.

This should only be done if your project page is not allowing you to save changes!

A. The Easy Way....

The following 4 steps can be done on the webpage or select all content in edit mode, copy and paste into a text editor. All steps must be completed before you attempt to save.

  1. In page edit mode, find all <pubmed> reference tags.
  2. Replace this tag with [http://www.ncbi.nlm.nih.gov/pubmed/ Note, there should be no spaces between the internet address and the pmid number.
  3. Now find all </pubmed> reference tags.
  4. Replace this second tag with ]

This will generate a numbered reference list that we can later fix up.


B. The Better Looking Result....

Whatever is between the <ref> </ref></pubmed> tags is what will appear in your reference list, so you can format the reference and link to appear in your reference list.

2011 Projects: Synaptic Junctions | Gap Junctions | Tight Junctions | Desmosomes | Adherens Junctions | Neuromuscular Junction