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Cells in vertebrate epithelia are held and linked together by '''cell-cell junctions'''.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> These direct interactions contribute to coordinated multicellular composition; they also enable the cells to tolerate and respond to different external forces that may cause disorder in epithelial tissues like lining in gut, skin outer layer etc.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
Cells in [[Vertebrate epithelia|vertebrate epithelia]] are held and linked together by cell-cell junctions<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. These direct interactions contribute to coordinated multicellular composition; they also enable the [[cells|cells]] to tolerate and respond to different external forces that may cause disorder in [[Epithelial|epithelial]] [[Tissue|tissues]] like lining in gut, [[Skin|skin]] outer layer etc.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


There are 3 major types of intercellular junctions. ''''Gap' junctions''', ''''Tight' junctions''', and ''''Anchoring' junctions '''which are further divided into two subdivisions: ''''Adherens Junctions' '''and''''Desmosomes''''.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> All these intercellular structures have one main feature in common; they link and adhere two adjacent cells together on the lateral side of their membranes via extremely diverse protein-made facilities.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref><br>Intercellular junctions occur in a broad range of locations in vertebrate body.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> In humans, anchoring junctions are found in tissues that stretch a lot, like muscles, heart and skin.<ref name="two">Yan HH, Mruk DD, Lee WM, Cheng CY (2008). "Cross-talk between tight and anchoring junctions-lesson from the testis". Adv. Exp. Med. Biol. 636: 234–54.</ref> Gap junctions are also found in heart muscle<ref name="three">"Abstracts: Proceedings of the International Gap Junction Conference. August 5–9, 2007. Elsinore, Denmark". Cell Commun. Adhes. 14 (6): 275–346. 2007.</ref>, and in the brain - contributing to vital processes like transferring signals<ref name="four">Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annu. Rev. Cell Dev. Biol. 20: 811–838.</ref>. They can also be found between retinal and skin cells.<ref name="three">"Abstracts: Proceedings of the International Gap Junction Conference. August 5–9, 2007. Elsinore, Denmark". Cell Commun. Adhes. 14 (6): 275–346. 2007.</ref><ref name="four">Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annu. Rev. Cell Dev. Biol. 20: 811–838.</ref> Tight junctions are present in tight and leaky epithelia.<ref name="five">Department, Biology. (2013) "Tight Junctions and other cellular connections". Davidson College. Available at: http://www.bio.davidson.edu/people/kabernd/berndcv/lab/epithelialinfoweb/Tight%20Junctions.html (Last accessed November 22 2015)</ref> For example, in kidneys, liver, the blood-brain barrier and CNS myelin sheath.<ref name="six">Gonzalez-Mariscal, L (2006) Tight Junctions, Austin: Springer US</ref>
There are 3 major types of intercellular junctions. '[[Gap Junction|Gap' junctions]], [[Tight junction|'Tight' junctions]], and 'Anchoring' junctions which are further divided into two subdivisions: [[Adherens Junctions|'Adherens Junctions']] and '[[Desmosomes|Desmosomes]]'<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. All these intercellular structures have one main feature in common; they link and adhere two adjacent cells together on the lateral side of their [[Membranes|membranes]] via extremely diverse [[Protein|protein]]-made facilities<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.  


Intercellular junctions take up particular positions in cell-cell interfaces.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> They're found between the apical and basal sides of epithelia.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> While the organisation of gap junctions is less regulated, the other 3 junctions are often found bundled together as''''Junctional Complex''''; where tight junctions are placed at the most apical region of epithelia, topping adherens junctions and desmosomes which are closer to the basal pole.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
Intercellular junctions occur in a broad range of locations in vertebrate body<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. In [[Humans|humans]], anchoring junctions are found in tissues that stretch a lot, like [[Muscles|muscles]], [[Heart|heart]] and [[Skin|skin]]<ref name="two">Yan HH, Mruk DD, Lee WM, Cheng CY (2008). "Cross-talk between tight and anchoring junctions-lesson from the testis". Adv. Exp. Med. Biol. 636: 234–54.</ref>. Gap junctions are also found in heart muscle<ref name="three">"Abstracts: Proceedings of the International Gap Junction Conference. August 5–9, 2007. Elsinore, Denmark". Cell Commun. Adhes. 14 (6): 275–346. 2007.</ref>., and in the [[Brain|brain]] - contributing to vital processes like transferring signals<ref name="four">Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annu. Rev. Cell Dev. Biol. 20: 811–838.</ref>.. They can also be found between retinal and skin cells<ref name="three">"Abstracts: Proceedings of the International Gap Junction Conference. August 5–9, 2007. Elsinore, Denmark". Cell Commun. Adhes. 14 (6): 275–346. 2007.</ref><ref name="four">Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annu. Rev. Cell Dev. Biol. 20: 811–838.</ref>. Tight junctions are present in tight and leaky epithelia<ref name="five">Department, Biology. (2013) "Tight Junctions and other cellular connections". Davidson College. Available at: http://www.bio.davidson.edu/people/kabernd/berndcv/lab/epithelialinfoweb/Tight%20Junctions.html (Last accessed November 22 2015)</ref>. For example, in [[Kidneys|kidneys]], [[Liver|liver]], the [[Blood-brain barrier|blood-brain barrier]] and [[Central nervous system|CNS]] [[Myelin sheath|myelin sheath]]<ref name="six">Gonzalez-Mariscal, L (2006) Tight Junctions, Austin: Springer US</ref>.


Adherens junctions and desmosomes are the 2 types of anchoring intercellular junctions.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> They both consist of a ''''Core Complex' '''which is made up of 2 major protein subunits<ref name="seven">Harris, Tony (2012) “Aherens Junctions: From Molecular Mechanism to Tissue Development and Disease”, Subcellular Biochemistry volume 60</ref>: 1.'''‘Cadherens’'''; transmembrane adhesive proteins that connect the two lateral sides of interacting membranes together via their extra cellular regions. Adherens junctions possess classical cadherens and desmosomes have non-classical cadherens.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Cadherens on the two sides of a junction are often the same or closely related, establishing a 'homophilic adhesion' which is the basis of their symmetric structure.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> 2.'''‘Catenins’'''; group of proteins that bind cytosolic sides of cadherens<ref name="seven">Harris, Tony (2012) “Aherens Junctions: From Molecular Mechanism to Tissue Development and Disease”, Subcellular Biochemistry volume 60</ref> and mediate their practical linkage to cell cytoskeleton.[1] In contrast, while in adherens junctions this linkage is made to actin cytoskeleton, catenins in desmosomes link cytosolic sides of cadherens to intermediate filaments of cytoskeleton, and that’s due to the different catenins involved.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> α, β, γ and p120 catenins serve adherens junctions, while desmosomes recruit α, plakophilin and desmoplakin catenins.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>
Intercellular junctions take up particular positions in cell-cell interfaces<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. They're found between the [[Apical membrane|apical]] and [[Basal lamina|basal]] sides of epithelia<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. While the organisation of gap junctions is less regulated, the other 3 junctions are often found bundled together as a 'Junctional Complex'; where tight


Anchoring junctions mechanically integrate interacting cells while having highly dynamic characteristics enabling them to readily react to signals from their surroundings and therefore enhancing remodelling of tissues during development.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref><ref name="hasht">Green, K.J., Jones, J.C.R. (1996) “Desmosomes and hemidesmosomes: structure and function of molecular components” FASEB J. 10, 871-881</ref>  
<span style="font-size: 13.28px;">junctions are placed at the most apical region of epithelia, topping adherens junctions and desmosomes which are closer to the basal pole<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.
</span> [[Image:Adhesive junction.png|right|Figure to show the general structure and binding between cadherins in a desmosome or adherens junction.]]
<div>Adherens junctions and desmosomes are the 2 types of anchoring intercellular junctions<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. They both consist of a 'Core Complex' which is made up of 2 major protein subunits<ref name="seven">Harris, Tony (2012) “Aherens Junctions: From Molecular Mechanism to Tissue Development and Disease”, Subcellular Biochemistry volume 60</ref>.: </div>
#‘Cadherens’; transmembrane adhesive proteins that connect the two lateral sides of interacting membranes together via their extracellular regions. Adherens junctions possess classical cadherins and desmosomes have non-classical cadherens<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. Cadherins on the two sides of a junction are often the same or closely related, establishing a 'homophilic adhesion' which is the basis of their symmetric structure<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.
#‘Catenins’; group of proteins that bind cytosolic sides of cadherens<ref name="seven">Harris, Tony (2012) “Aherens Junctions: From Molecular Mechanism to Tissue Development and Disease”, Subcellular Biochemistry volume 60</ref>. and mediate their practical linkage to cell cytoskeleton. In contrast, while in adherens junctions this linkage is made to [[Actin|actin]] [[Cytoskeleton|cytoskeleton]], catenins in desmosomes link [[Cytosol|cytosolic]] sides of cadherins to [[Intermediate filaments|intermediate filaments]] of the cytoskeleton, and that’s due to the different catenins involved<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. α, β, γ and p120 catenins serve adherens junctions, while desmosomes recruit α, plakophilin and desmoplakin catenins<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


Tight junctions share some structural features with anchoring junctions.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> By definition, they are continuous intercellular adhesive contact points that form barriers able to discriminate between different particles in paracellular space amid two adjacent epithelial cells.<ref name="six">Gonzalez-Mariscal, L (2006) Tight Junctions, Austin: Springer US</ref> Homophilic adhesion of transmembrane proteins implanted in each of the two lateral membranes in these junctions is how they're structured; which is just like the pattern by which anchoring junctions are assembled.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> However, a completely different family of proteins called''''Claudins' '''play this role of cell-cell adhesion here.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Numerous claudin-claudin contact points make up 'Sealing Strands', establishing an extensive network to obstruct diffusion of macromolecules.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
Anchoring junctions mechanically integrate interacting cells while having highly dynamic characteristics enabling them to readily react to signals from their surroundings and therefore enhancing remodelling of tissues during development<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref><ref name="hasht">Green, K.J., Jones, J.C.R. (1996) “Desmosomes and hemidesmosomes: structure and function of molecular components” FASEB J. 10, 871-881</ref>.


Permeability of tight junctions can be directed by different claudin combinations.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> A family of large scaffold proteins called ''''Zonula Occludins' '''or ''''ZO'''', which are not necessary for assembly of tight junctions, are further bound to intracellular sides of claudins to limit and specialise junctional permeability.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
Hemidesmosomes are also a type of anchoring intercellular junction and provide attachment of cells to the extracellular martix<ref>Wheater’s Functional Histology 6th edition, Barbara Young, Geraldine O’Dowd, Phillip Woodford, Edinburgh: Churchill Livingstone 2014 pg(89)</ref>. Integrins are the main protein subunit of Hemidesmosomes, more specifically it is alpha6beta4 integrin which is most crucial as it forms a cell membrane-embedded complex, therefore the function of hemidesmosomes is to connect between Lamin-332 located on the extracellular matrix and the alpha6beta4 on the cells allowing the cells to anchor intermediate filaments located on the extracellular matrix<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452579/ Molecular architecture and function of the hemidesmosome, Gernot Walko, Maria J. Castañón, and Gerhard Wiche, Published May 29th 2015; 360(3): 529-544</ref>.


Another structural similarity between tight and anchoring junctions is that they both require additional intracellular proteins that bind the cytosolic region of adhesion proteins (claudins in tight junctions and cadherens in anchoring junctions).<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Catenins accomplish this task in anchoring junctions, and in tight junctions, occludins mediate linkage of tight junction transmembrane adhesive proteins to the cytoplasm of their corresponding cells.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> The network provided by occludins ultimately links claudins to actin cytoskeleton, just like adherens junctions.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
Tight junctions share some structural features with anchoring junctions<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. By definition, they are continuous intercellular adhesive contact points that form barriers able to discriminate between different particles in paracellular space amid two adjacent epithelial cells<ref name="six">Gonzalez-Mariscal, L (2006) Tight Junctions, Austin: Springer US</ref>. Homophilic adhesion of transmembrane proteins implanted in each of the two lateral membranes in these junctions is how they're structured; which is just like the pattern by which anchoring junctions are assembled<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. However, a completely different family of proteins called 'Claudins' play this role of cell-cell adhesion here<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.Claudins are tetraspan proteins meaning they have four transmembrane domains.They form two extracellular loops in the paracellular space, the first comprising of 41-45 amino acids and 10-21 in the second loop<ref>Anderson J.M., Van Itallie C.M. (2006) Tight Junction Channels. In: Tight Junctions. Springer, Boston, MA.</ref>. These small loops form the very small (4Å radius) pores which are able to form a protective barrier that is highly selective and maintains osmotic ballance<ref>Department, Biology. "Tight Junctions (and other cellular connections)". Davidson College. Retrieved 2015-01-12</ref>. Numerous claudin-claudin contact points make up 'Sealing Strands', establishing an extensive network to obstruct diffusion of [[Macromolecules|macromolecules]]<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


Gap junctions mediate a direct connection between cytoplasm of two adjacent cells.<ref name="noh">Lampe, Paul D., Lau, Alan F. (2004). "The effects of connexin phosphorylation on gap junctional communication". The international journal of biochemistry &amp;amp;amp;amp;amp; cell biology 36 (7): 1171–1186.</ref> <br>A gap junction channel is formed by 2 '''connexon''' structures on each side of the junction, each consisting of 6 '''connexin proteins''', passing through the membrane 4 times.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Gap junctions are composed of many of such channels forming a sort of molecular filter that can have selective permeability for and against different particles.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
The permeability of tight junctions can be directed by different claudin combinations<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. A family of large scaffold proteins called 'Zonula Occludins' or 'ZO', which are not necessary for assembly of tight junctions, are further bound to intracellular sides of claudins to limit and specialise junctional permeability<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


While gap junctions share a common feature with all other junctions discussed earlier - producing a cell-cell adhesive connection-, providing the two adjacent interacting cells with a communicative channel is what makes them completely different from anchoring junctions, and even tight junctions.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Although tight junctions do act as selective sieves, or 'pores', they do so through ''''paracellular' '''pathway<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>, i.e. Passing down the intercellular space, located between the cells.<ref name="dah">Medical Dictionary. (2009). Available at: http://medical-dictionary.thefreedictionary.com/paracellular (Last accessed November 22 2015)</ref>  
Another structural similarity between tight and anchoring junctions is that they both require additional intracellular proteins that bind the cytosolic region of adhesion proteins (claudins in tight junctions and cadherins in anchoring junctions)<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. Catenins accomplish this task in anchoring junctions, and in tight junctions, occludins mediate linkage of tight junction [[Transmembrane|transmembrane]] adhesive proteins to the cytoplasm of their corresponding cells<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. The network provided by occludins ultimately links claudins to actin cytoskeleton, just like adherens junctions<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


A remarkable similarity between gap junctions and anchoring junctions is that plaques of gap junctions also have a high dynamicity and are able to promptly assemble, disassemble or proceed remodelling, for example, to remove aged connexons from the junction.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
Gap junctions mediate a direct connection between the cytoplasm of two adjacent cells<ref name="noh">Lampe, Paul D., Lau, Alan F. (2004). "The effects of connexin phosphorylation on gap junctional communication". The international journal of biochemistry and cell biology 36 (7): 1171–1186.</ref>.


Gap junctions can have customisable permeability by having different combinations of connexin proteins forming their connexon hemichannels.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> The connexons can even be asymmetrical and have non-identical 'half channels' on each side, which is contrary to the symmetrical nature of anchoring junctions - their assembly being based on homophilic attractions and symmetry.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
A gap junction channel is formed by 2 connexon structures on each side of the junction, each consisting of 6 connexin proteins, passing through the membrane 4 times<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. Gap junctions are composed of many of such channels forming a sort of molecular filter that can have selective permeability for and against different particles<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


Although tight junctions act to seal the paracellular space, they allow certain ions and water to pass through them.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Having different claudins in their composition leads to different types of selectivity.<ref name="yazdah">M. Krug, S., D. Schulzke, J., Fromm M. (2014) “Tight junction, selective permeability, and related diseases”. Seminars in Cell &amp;amp;amp;amp;amp; Developmental Biology. Volume 36, Pages 166–176</ref> For example, claudin -10b shows cation selectivity, while claudin -10a shows anion selectivity.<ref name="yazdah">M. Krug, S., D. Schulzke, J., Fromm M. (2014) “Tight junction, selective permeability, and related diseases”. Seminars in Cell &amp;amp;amp;amp;amp; Developmental Biology. Volume 36, Pages 166–176</ref> On the other hand, gap junctions allow a wider range of compounds to pass through; in addition to inorganic ions and water, they basically are permeable to all other water solute molecules not heavier than 1000Da, including sugars, amino acids, nucleotides and vitamins.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
While gap junctions share a common feature with all other junctions discussed earlier - producing a cell-cell adhesive connection-, providing the two adjacent interacting cells with a communicative channel is what makes them completely different from anchoring junctions, and even tight junctions<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. Although tight junctions do act as selective sieves, or 'pores', they do so through 'paracellular' pathway<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>, i.e. Passing down the intercellular space, located between the cells<ref name="dah">Medical Dictionary. (2009). Available at: http://medical-dictionary.thefreedictionary.com/paracellular (Last accessed November 22 2015)</ref>.


In conclusion, despite having different functions, the fact that all the structures mentioned above provide cells they’re connected to with a form of cohesion and connection is their clearest similarity, a feature of crucial importance.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref> Similarities do occur in structure; like how anchoring and tight junctions are linked to cell cytoskeleton, and in function; like how both tight and gap junctions act as permeable surfaces. But there are also fundamental differences to consider, most notably the completely different proteins forming them, and their overall function.<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>  
A remarkable similarity between gap junctions and anchoring junctions is that plaques of gap junctions also have a high dynamicity and are able to promptly assemble, disassemble or proceed remodelling, for example, to remove aged connexons from the junction<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


<br>
Gap junctions can have customisable permeability by having different combinations of connexin proteins forming their connexon hemichannels<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. The connexons can even be asymmetrical and have non-identical 'half channels' on each side, which is contrary to the symmetrical nature of anchoring junctions - their assembly being based on homophilic attractions and symmetry<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


<br>
Although tight junctions act to seal the paracellular space, they allow certain [[Ions|ions]] and [[Water|water]] to pass through them<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. Having different claudins in their composition leads to different types of selectivity<ref name="yazdah">M. Krug, S., D. Schulzke, J., Fromm M. (2014) “Tight junction, selective permeability, and related diseases”. Seminars in Cell and Developmental Biology. Volume 36, Pages 166–176</ref>. For example, claudin -10b shows cation selectivity, while claudin -10a shows anion selectivity<ref name="yazdah">M. Krug, S., D. Schulzke, J., Fromm M. (2014) “Tight junction, selective permeability, and related diseases”. Seminars in Cell and Developmental Biology. Volume 36, Pages 166–176</ref>. On the other hand, gap junctions allow a wider range of compounds to pass through; in addition to inorganic ions and water, they basically are permeable to all other water solute molecules not heavier than 1000 [[Dalton|Da]], including [[Sugars|sugars]], [[Amino acids|amino acids]], [[Nucleotides|nucleotides]] and [[Vitamins|vitamins]]<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


<br>
Intercellular Junctions also occur in plants the main type of intercellular junction in plants are the plasmadesma<ref>https://www.ncbi.nlm.nih.gov/books/NBK26857/ content from Molecular Biology of the cell, 4th edition, Alberts B, Johnson A, Lewis J, et al. New York Garland science, 2002</ref>. Plasmodesmata are similar in structure to gap junctions as they form channels between adjacent plant cells, the structure of the channel consists of a desmotubule which runs between the cell and is itself surrounded by a cytoplasmic ring called the annulus<ref>The world of the cell 7th edition, Wayne M Becker, Lewis J kleinsmith, Jeff Hardin, Gregory Paul Bertoni, Pearson Benjamin cummings publishing, 2009 pg 484, 489, (502-504)</ref>. The function of plasmodesmata is to allow the transfer of Ions, RNA, transcriptional factors and other small hydrophobic molecules between adjacent plant cells<ref>The world of the cell 7th edition, Wayne M Becker, Lewis J kleinsmith, Jeff Hardin, Gregory Paul Bertoni, Pearson Benjamin cummings publishing, 2009 pg 484, 489, (502-504)</ref>. Therefore, plasmodesmata allow communication to occur between plants cells by chemical communication<ref>The world of the cell 7th edition, Wayne M Becker, Lewis J kleinsmith, Jeff Hardin, Gregory Paul Bertoni, Pearson Benjamin cummings publishing, 2009 pg 484, 489, (502-504)</ref>.


'''<br>'''
In conclusion, despite having different functions, the fact that all the structures mentioned above allow cells to form of cohesion and connection is their clearest similarity, a feature of crucial importance<ref name="mboc">Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>. Similarities do occur in structure; like how anchoring and tight junctions are linked to cell cytoskeleton, and in function; like how both tight and gap junctions act as permeable surfaces. But there are also fundamental differences to consider, most notably the completely different proteins forming them, and their overall function<ref name="mboc">Alberts et al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science</ref>.


'''References<br>'''
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Latest revision as of 09:20, 5 December 2017

Cells in vertebrate epithelia are held and linked together by cell-cell junctions[1]. These direct interactions contribute to coordinated multicellular composition; they also enable the cells to tolerate and respond to different external forces that may cause disorder in epithelial tissues like lining in gut, skin outer layer etc.[1].

There are 3 major types of intercellular junctions. 'Gap' junctions, 'Tight' junctions, and 'Anchoring' junctions which are further divided into two subdivisions: 'Adherens Junctions' and 'Desmosomes'[1]. All these intercellular structures have one main feature in common; they link and adhere two adjacent cells together on the lateral side of their membranes via extremely diverse protein-made facilities[1].

Intercellular junctions occur in a broad range of locations in vertebrate body[1]. In humans, anchoring junctions are found in tissues that stretch a lot, like muscles, heart and skin[2]. Gap junctions are also found in heart muscle[3]., and in the brain - contributing to vital processes like transferring signals[4].. They can also be found between retinal and skin cells[3][4]. Tight junctions are present in tight and leaky epithelia[5]. For example, in kidneys, liver, the blood-brain barrier and CNS myelin sheath[6].

Intercellular junctions take up particular positions in cell-cell interfaces[1]. They're found between the apical and basal sides of epithelia[1]. While the organisation of gap junctions is less regulated, the other 3 junctions are often found bundled together as a 'Junctional Complex'; where tight

junctions are placed at the most apical region of epithelia, topping adherens junctions and desmosomes which are closer to the basal pole[1].

Figure to show the general structure and binding between cadherins in a desmosome or adherens junction.
Figure to show the general structure and binding between cadherins in a desmosome or adherens junction.
Adherens junctions and desmosomes are the 2 types of anchoring intercellular junctions[1]. They both consist of a 'Core Complex' which is made up of 2 major protein subunits[7].:
  1. ‘Cadherens’; transmembrane adhesive proteins that connect the two lateral sides of interacting membranes together via their extracellular regions. Adherens junctions possess classical cadherins and desmosomes have non-classical cadherens[1]. Cadherins on the two sides of a junction are often the same or closely related, establishing a 'homophilic adhesion' which is the basis of their symmetric structure[1].
  2. ‘Catenins’; group of proteins that bind cytosolic sides of cadherens[7]. and mediate their practical linkage to cell cytoskeleton. In contrast, while in adherens junctions this linkage is made to actin cytoskeleton, catenins in desmosomes link cytosolic sides of cadherins to intermediate filaments of the cytoskeleton, and that’s due to the different catenins involved[1]. α, β, γ and p120 catenins serve adherens junctions, while desmosomes recruit α, plakophilin and desmoplakin catenins[1].

Anchoring junctions mechanically integrate interacting cells while having highly dynamic characteristics enabling them to readily react to signals from their surroundings and therefore enhancing remodelling of tissues during development[1][8].

Hemidesmosomes are also a type of anchoring intercellular junction and provide attachment of cells to the extracellular martix[9]. Integrins are the main protein subunit of Hemidesmosomes, more specifically it is alpha6beta4 integrin which is most crucial as it forms a cell membrane-embedded complex, therefore the function of hemidesmosomes is to connect between Lamin-332 located on the extracellular matrix and the alpha6beta4 on the cells allowing the cells to anchor intermediate filaments located on the extracellular matrix[10].

Tight junctions share some structural features with anchoring junctions[1]. By definition, they are continuous intercellular adhesive contact points that form barriers able to discriminate between different particles in paracellular space amid two adjacent epithelial cells[6]. Homophilic adhesion of transmembrane proteins implanted in each of the two lateral membranes in these junctions is how they're structured; which is just like the pattern by which anchoring junctions are assembled[1]. However, a completely different family of proteins called 'Claudins' play this role of cell-cell adhesion here[1].Claudins are tetraspan proteins meaning they have four transmembrane domains.They form two extracellular loops in the paracellular space, the first comprising of 41-45 amino acids and 10-21 in the second loop[11]. These small loops form the very small (4Å radius) pores which are able to form a protective barrier that is highly selective and maintains osmotic ballance[12]. Numerous claudin-claudin contact points make up 'Sealing Strands', establishing an extensive network to obstruct diffusion of macromolecules[1].

The permeability of tight junctions can be directed by different claudin combinations[1]. A family of large scaffold proteins called 'Zonula Occludins' or 'ZO', which are not necessary for assembly of tight junctions, are further bound to intracellular sides of claudins to limit and specialise junctional permeability[1].

Another structural similarity between tight and anchoring junctions is that they both require additional intracellular proteins that bind the cytosolic region of adhesion proteins (claudins in tight junctions and cadherins in anchoring junctions)[1]. Catenins accomplish this task in anchoring junctions, and in tight junctions, occludins mediate linkage of tight junction transmembrane adhesive proteins to the cytoplasm of their corresponding cells[1]. The network provided by occludins ultimately links claudins to actin cytoskeleton, just like adherens junctions[1].

Gap junctions mediate a direct connection between the cytoplasm of two adjacent cells[13].

A gap junction channel is formed by 2 connexon structures on each side of the junction, each consisting of 6 connexin proteins, passing through the membrane 4 times[1]. Gap junctions are composed of many of such channels forming a sort of molecular filter that can have selective permeability for and against different particles[1].

While gap junctions share a common feature with all other junctions discussed earlier - producing a cell-cell adhesive connection-, providing the two adjacent interacting cells with a communicative channel is what makes them completely different from anchoring junctions, and even tight junctions[1]. Although tight junctions do act as selective sieves, or 'pores', they do so through 'paracellular' pathway[1], i.e. Passing down the intercellular space, located between the cells[14].

A remarkable similarity between gap junctions and anchoring junctions is that plaques of gap junctions also have a high dynamicity and are able to promptly assemble, disassemble or proceed remodelling, for example, to remove aged connexons from the junction[1].

Gap junctions can have customisable permeability by having different combinations of connexin proteins forming their connexon hemichannels[1]. The connexons can even be asymmetrical and have non-identical 'half channels' on each side, which is contrary to the symmetrical nature of anchoring junctions - their assembly being based on homophilic attractions and symmetry[1].

Although tight junctions act to seal the paracellular space, they allow certain ions and water to pass through them[1]. Having different claudins in their composition leads to different types of selectivity[15]. For example, claudin -10b shows cation selectivity, while claudin -10a shows anion selectivity[15]. On the other hand, gap junctions allow a wider range of compounds to pass through; in addition to inorganic ions and water, they basically are permeable to all other water solute molecules not heavier than 1000 Da, including sugars, amino acids, nucleotides and vitamins[1].

Intercellular Junctions also occur in plants the main type of intercellular junction in plants are the plasmadesma[16]. Plasmodesmata are similar in structure to gap junctions as they form channels between adjacent plant cells, the structure of the channel consists of a desmotubule which runs between the cell and is itself surrounded by a cytoplasmic ring called the annulus[17]. The function of plasmodesmata is to allow the transfer of Ions, RNA, transcriptional factors and other small hydrophobic molecules between adjacent plant cells[18]. Therefore, plasmodesmata allow communication to occur between plants cells by chemical communication[19].

In conclusion, despite having different functions, the fact that all the structures mentioned above allow cells to form of cohesion and connection is their clearest similarity, a feature of crucial importance[1]. Similarities do occur in structure; like how anchoring and tight junctions are linked to cell cytoskeleton, and in function; like how both tight and gap junctions act as permeable surfaces. But there are also fundamental differences to consider, most notably the completely different proteins forming them, and their overall function[1].

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 Alberts et. al. (2015) Molecular Biology of The Cell, 6th edition, New York: Garland Science Cite error: Invalid <ref> tag; name "mboc" defined multiple times with different content
  2. ↑ Yan HH, Mruk DD, Lee WM, Cheng CY (2008). "Cross-talk between tight and anchoring junctions-lesson from the testis". Adv. Exp. Med. Biol. 636: 234–54.
  3. ↑ 3.0 3.1 "Abstracts: Proceedings of the International Gap Junction Conference. August 5–9, 2007. Elsinore, Denmark". Cell Commun. Adhes. 14 (6): 275–346. 2007.
  4. ↑ 4.0 4.1 Wei CJ, Xu X, Lo CW (2004). "Connexins and cell signaling in development and disease". Annu. Rev. Cell Dev. Biol. 20: 811–838.
  5. ↑ Department, Biology. (2013) "Tight Junctions and other cellular connections". Davidson College. Available at: http://www.bio.davidson.edu/people/kabernd/berndcv/lab/epithelialinfoweb/Tight%20Junctions.html (Last accessed November 22 2015)
  6. ↑ 6.0 6.1 Gonzalez-Mariscal, L (2006) Tight Junctions, Austin: Springer US
  7. ↑ 7.0 7.1 Harris, Tony (2012) “Aherens Junctions: From Molecular Mechanism to Tissue Development and Disease”, Subcellular Biochemistry volume 60
  8. ↑ Green, K.J., Jones, J.C.R. (1996) “Desmosomes and hemidesmosomes: structure and function of molecular components” FASEB J. 10, 871-881
  9. ↑ Wheater’s Functional Histology 6th edition, Barbara Young, Geraldine O’Dowd, Phillip Woodford, Edinburgh: Churchill Livingstone 2014 pg(89)
  10. ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452579/ Molecular architecture and function of the hemidesmosome, Gernot Walko, Maria J. Castañón, and Gerhard Wiche, Published May 29th 2015; 360(3): 529-544
  11. ↑ Anderson J.M., Van Itallie C.M. (2006) Tight Junction Channels. In: Tight Junctions. Springer, Boston, MA.
  12. ↑ Department, Biology. "Tight Junctions (and other cellular connections)". Davidson College. Retrieved 2015-01-12
  13. ↑ Lampe, Paul D., Lau, Alan F. (2004). "The effects of connexin phosphorylation on gap junctional communication". The international journal of biochemistry and cell biology 36 (7): 1171–1186.
  14. ↑ Medical Dictionary. (2009). Available at: http://medical-dictionary.thefreedictionary.com/paracellular (Last accessed November 22 2015)
  15. ↑ 15.0 15.1 M. Krug, S., D. Schulzke, J., Fromm M. (2014) “Tight junction, selective permeability, and related diseases”. Seminars in Cell and Developmental Biology. Volume 36, Pages 166–176
  16. ↑ https://www.ncbi.nlm.nih.gov/books/NBK26857/ content from Molecular Biology of the cell, 4th edition, Alberts B, Johnson A, Lewis J, et al. New York Garland science, 2002
  17. ↑ The world of the cell 7th edition, Wayne M Becker, Lewis J kleinsmith, Jeff Hardin, Gregory Paul Bertoni, Pearson Benjamin cummings publishing, 2009 pg 484, 489, (502-504)
  18. ↑ The world of the cell 7th edition, Wayne M Becker, Lewis J kleinsmith, Jeff Hardin, Gregory Paul Bertoni, Pearson Benjamin cummings publishing, 2009 pg 484, 489, (502-504)
  19. ↑ The world of the cell 7th edition, Wayne M Becker, Lewis J kleinsmith, Jeff Hardin, Gregory Paul Bertoni, Pearson Benjamin cummings publishing, 2009 pg 484, 489, (502-504)
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