Claudin: Difference between revisions - Wikipedia

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{{Short description|Group of proteins forming tight junctions between cells}}

{{about|for-multi|the Arthurian character|Prince Claudin|the French composer|Claudin de Sermisy}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

[[File:Cellular_tight_junction-en.svg|thumb|300px]]

'''Claudins''' are a family of [[protein]]s which, along with [[occludin]], are the most important components of the [[tight junction]]s ([[Tight junction|zonulae occludentes]]).<ref name=":0">{{cite book | vauthors = Hou J, Konrad M | chapter = Chapter 7 - Claudins and Renal Magnesium Handling|date=2010-01-01 |title = Current Topics in Membranes|volume=65|pages=151–176| veditors = Yu AS |publisher=Academic Press|language=en|doi=10.1016/s1063-5823(10)65007-7 | isbn = 9780123810397}}</ref><ref>{{cite book | vauthors = Furuse M | chapter = Chapter 1 - Introduction: Claudins, Tight Junctions, and the Paracellular Barrier|date=2010-01-01 | title = Current Topics in Membranes|volume=65|pages=1–19| veditors = Yu AS |publisher=Academic Press|language=en|doi=10.1016/s1063-5823(10)65001-6 | isbn = 9780123810397}}</ref> Tight junctions establish the [[paracellular]] barrier that controls the flow of molecules in the intercellular space between the cells of an [[epithelium]].<ref name=":0" /><ref>{{cite book | vauthors = Szaszi K, Amoozadeh Y | chapter = Chapter Six - New Insights into Functions, Regulation, and Pathological Roles of Tight Junctions in Kidney Tubular Epithelium|date=2014-01-01 | title = International Review of Cell and Molecular Biology|volume=308|pages=205–271| veditors = Jeon KW |publisher=Academic Press|language=en|doi=10.1016/b978-0-12-800097-7.00006-3 | pmid = 24411173| isbn = 9780128000977}}</ref><ref>{{cite journal | vauthors = Otani T, Nguyen TP, Tokuda S, Sugihara K, Sugawara T, Furuse K, Miura T, Ebnet K, Furuse M | title = Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity | journal = The Journal of Cell Biology | volume = 218 | issue = 10 | pages = 3372–3396 | date = October 2019 | pmid = 31467165 | pmc = 6781433 | doi = 10.1083/jcb.201812157 }}</ref> They have four transmembrane domains, with the [[N-terminus]] and the C-terminus in the cytoplasm.

'''Claudins''' are a family of [[protein]]s that are the most important components of the [[tight junction]]s, where they establish the [[paracellular]] barrier that controls the flow of molecules in the intercellular space between the cells of an [[epithelium]]. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm.

== Structure ==

Claudins are small (20–2720–24/27 [[Atomic mass unit|kilodalton]] (kDa))<ref name=":1">{{cite book| vauthors = Greene C, Campbell M, Janigro D | chapter = Chapter 1 - Fundamentals of Brain–Barrier Anatomy and Global Functions|date=2019-01-01| title = Nervous System Drug Delivery|pages=3–20| veditors = Lonser RR, Sarntinoranont M, Bankiewicz K |publisher=Academic Press|language=en|doi=10.1016/b978-0-12-813997-4.00001-3|isbn=978-0-12-813997-4 | s2cid = 198273920}}</ref> [[transmembrane protein]]s which are found in many [[organisms]], ranging from [[nematode]]s to [[human]] beings,. andThey areall have a very similar in their structure, although this conservation is not observed on the [[Conservation (genetics)|genetic level]]. Claudins span the cellular membrane 4 times, with the [[N-terminal end]] and the [[C-terminal end]] both located in the [[cytoplasm]], and two extracellular loops which show the highest degree of conservation. The first extracellular loop consists on average of 53 [[amino acid]]s and the second one, being slightly smaller, of 24 amino acids. The N-terminal end is usually very short (4–10 amino acids), the C-terminal end varies in length from 21 to 63 and is necessary for the localisation of these proteins in the tight junctions.<ref>{{cite journal |author=Rüffer C, Gerke V |title=The C-terminal cytoplasmic tail of claudins 1 and 5 but not its PDZ-binding motif is required for apical localization at epithelial and endothelial tight junctions |journal=Eur. J. Cell Biol. |volume=83 |issue=4 |pages=135–44 |year=2004 |month=May |pmid=15260435 }}</ref> It is suspected that the [[cysteine]]s of individual or separate claudins form [[disulfide bonds]]. All human [[claudins]] (with the exception of Claudin 12) have domains that let them bind to [[PDZ domain]]s of [[scaffold protein]]s.

Claudins have both cis and trans interactions between cell membranes.<ref>{{cite book| vauthors = Haseloff RF, Piontek J, Blasig IE | chapter = Chapter 5 - The Investigation of cis- and trans-Interactions Between Claudins|date=2010-01-01 | title = Current Topics in Membranes|volume=65|pages=97–112| veditors = Yu AS |publisher=Academic Press|language=en|doi=10.1016/s1063-5823(10)65005-3 | isbn = 9780123810397}}</ref> Cis-interactions is when claudins on the same membrane interact, one way they interact is by transmembrane domain having molecular interactions.<ref name=":2">{{cite journal | vauthors = Günzel D, Yu AS | title = Claudins and the modulation of tight junction permeability | journal = Physiological Reviews | volume = 93 | issue = 2 | pages = 525–569 | date = April 2013 | pmid = 23589827 | pmc = 3768107 | doi = 10.1152/physrev.00019.2012 }}</ref> Trans-interaction is when claudins of neighboring cells interact through their extracellular loops.<ref name=":3">{{Cite journal|date=September 2010|title=Crystal Structures of claudins: insights into their intermolecular interactions|url=https://doi.org/10.1111/nyas.2010.1205.issue-s1|journal=Annals of the New York Academy of Sciences|volume=1205|doi=10.1111/nyas.2010.1205.issue-s1|issn=0077-8923|url-access=subscription}}</ref> Cis-interactions is also known as side-to-side interactions and trans-interactions is also known as head-to-head interactions.<ref name=":6">{{cite journal | vauthors = Fuladi S, Jannat RW, Shen L, Weber CR, Khalili-Araghi F | title = Computational Modeling of Claudin Structure and Function | journal = International Journal of Molecular Sciences | volume = 21 | issue = 3 | pages = 742 | date = January 2020 | pmid = 31979311 | pmc = 7037046 | doi = 10.3390/ijms21030742 | doi-access = free }}</ref>

Generally the tight junction is known for its impermeability. However, depending on the type of claudin and their interactions there is selective permeability. This includes charge selectivity and size selectivity.<ref name=":2" />

=== N-terminal ===

The N-terminal end is usually very short (1–10 amino acids)<ref name=":4" /><ref name=":3" /> It is located in the cytoplasm where it is thought to help to contribute to cell signaling, cytoskeletal organization and other possible functions.<ref name=":5">{{cite journal | vauthors = Tsukita S, Tanaka H, Tamura A | title = The Claudins: From Tight Junctions to Biological Systems | language = English | journal = Trends in Biochemical Sciences | volume = 44 | issue = 2 | pages = 141–152 | date = February 2019 | pmid = 30665499 | doi = 10.1016/j.tibs.2018.09.008 | s2cid = 58640701 | doi-access = free }}</ref>

=== C-terminal ===

The C-terminal has a longer chain and is located in the cytoplasm. It varies in length from 21 to 63 and is necessary for the localization of these proteins in the tight junctions.<ref name=":4">{{cite journal | vauthors = Rüffer C, Gerke V | title = The C-terminal cytoplasmic tail of claudins 1 and 5 but not its PDZ-binding motif is required for apical localization at epithelial and endothelial tight junctions | journal = European Journal of Cell Biology | volume = 83 | issue = 4 | pages = 135–144 | date = May 2004 | pmid = 15260435 | doi = 10.1078/0171-9335-00366 }}</ref> It is thought that it may play a role in cell signaling.<ref name=":5" /> All human claudins (with the exception of Claudin 12) have domains that let them bind to [[PDZ domain]]s of [[scaffold protein]]s.

=== Transmembrane domain ===

The [[transmembrane domain]] is the amino acids that cross the cellular membrane. The transmembrane domain is important for cis-interaction of claudins.

=== First extracellular loop ===

The first extracellular loop has a range of 42-56 amino acids and is longer than the second extracellular loop. It is suspected that the [[cysteine]]s of found on the first extracellular loop form [[disulfide bonds]]. This loop has charged amino acids that may be the predictor for the charge selectivity of tight junctions. The first extracellular loop plays a role in trans-interaction of claudins of adjacent cells.<ref name=":2" />

=== Second extracellular loop ===

The second extracellular loop is shorter than the first extracellular loop. In this short chain of amino acids there are three hydrophobic residues. These three residues are suspected to be a contributor to the trans-interaction of proteins between adjacent cells.<ref name=":2" />

==History==

Claudins were first named in 1998 by Japanese researchers Mikio Furuse and Shoichiro Tsukita at [[Kyoto University]].<ref>

{{cite journal |author vauthors = Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S | title = Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to [[occludin]] | journal =J. The Journal of Cell Biol.Biology | volume = 141 | issue = 7 | pages=1539–50 |year=1998 1539–1550 |month date = June 1998 | pmid = 9647647 | pmc = 2132999 |url=http://www.jcb.org/cgi/pmidlookup?view=long&pmid=9647647 |doi = 10.1083/jcb.141.7.1539 }}

</ref> The name ''claudin'' comes from [[Latin]] word ''claudere'' ("to close"), suggesting the barrier role of these proteins.

=== Studies ===

A recent review discusses evidence regarding the structure and function of claudin family proteins using a systems approach to understand evidence generated by [[proteomics]] techniques.<ref>

{{cite journal | vauthors = Liu F, Koval M, Ranganathan S, Fanayan S, Hancock WS, Lundberg EK, Beavis RC, Lane L, Duek P, McQuade L, Kelleher NL, Baker MS | title = Systems Proteomics View of the Endogenous Human Claudin Protein Family | journal = Journal of Proteome Research | volume = 15 | issue = 2 | pages = 339–359 | date = February 2016 | pmid = 26680015 | pmc = 4777318 | doi = 10.1021/acs.jproteome.5b00769 }}

</ref>

A chimeric claudin was synthesized to help enhance the understanding of both the structure and function of the tight junction.<ref name=":7">{{cite journal | vauthors = Taylor A, Warner M, Mendoza C, Memmott C, LeCheminant T, Bailey S, Christensen C, Keller J, Suli A, Mizrachi D | title = Chimeric Claudins: A New Tool to Study Tight Junction Structure and Function | journal = International Journal of Molecular Sciences | volume = 22 | issue = 9 | pages = 4947 | date = May 2021 | pmid = 34066630 | pmc = 8124314 | doi = 10.3390/ijms22094947 | doi-access = free }}</ref>

Computational modeling is also another technique being used to help enhance research into the structure and functions of claudins.<ref name=":6" />

==Genes==

{{Infobox protein family

In humans, 24 members of the family have been described.

| Symbol = PMP22_Claudin

| Name = PMP22_Claudin

| image =

| width =

| caption =

| Pfam = PF00822

| Pfam_clan = CL0375

| InterPro = IPR004031

| SMART =

| PROSITE = PDOC01045

| MEROPS =

| SCOP =

| TCDB = 1.H.1

| OPM family = 194

| OPM protein = 4p79

| CAZy =

| CDD =

}}

There are 23 genes found in the human genome for claudin proteins<ref name=":7" /> and there are 27 transmembrane domains across mammals.<ref name=":3" /><ref name=":5" /> The conservation is not observed on a [[Conserved sequence|genetic level]]. Despite the genetic level not being conserved across claudins their structural conservation are very similar.

* ''[[CLDN1]]'', ''[[CLDN2]]'', ''[[CLDN3]]'', ''[[CLDN4]]'', ''[[CLDN5]]'', ''[[CLDN6]]'', ''[[CLDN7]]'', ''[[CLDN8]]'', ''[[CLDN9]]'', ''[[CLDN10]]'',<ref>{{cite book | vauthors = Hou J | chapter = Chapter 7 - Paracellular Channel in Organ System|date=2019-01-01 | title = The Paracellular Channel|pages=93–141 | veditors = Hou J |publisher=Academic Press|language=en|doi=10.1016/b978-0-12-814635-4.00007-3|isbn=978-0-12-814635-4 | s2cid = 90477792}}</ref> ''[[CLDN11]]'', ''[[CLDN12]]'', ''[[CLDN13]]'', ''[[CLDN14]]'', ''[[CLDN15]]'', ''[[CLDN16]]'', ''[[CLDN17]]'', ''[[CLDN18]]'', ''[[CLDN19]]'',<ref>{{cite book | vauthors = Hou J | chapter = Chapter 8 - Paracellular Channel in Human Disease|date=2019-01-01 |title = The Paracellular Channel|pages=143–173| veditors = Hou J |publisher=Academic Press|language=en|doi=10.1016/b978-0-12-814635-4.00008-5|isbn=978-0-12-814635-4| s2cid = 90122806}}</ref> ''[[CLDN20]]'', ''[[CLDN21]]'', ''[[CLDN22]]'', ''[[CLDN23]]''

== See also ==

* [[Occludin]]

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== References ==

{{Reflist}}

<references/>

{{Epithelial tissue}}

{{Authority control}}

[[Category:Cell adhesion proteins]]

[[Category:Structural proteins]]

{{Link FA|de}}

[[fr:Jonction serrée#Claudines]]