{{Short description|Group of proteins forming tight junctions between cells}} {{for-multi|the Arthurian character|Prince Claudin|the French composer|Claudin de Sermisy}} {{cs1 config|name-list-style=vanc|display-authors=6}}
thumb|300px '''Claudins''' are a family of proteins which, along with occludin, are the most important components of the tight junctions (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.
== Structure == thumb|transmembrane domains of claudin-1 Claudins are small (20–24/27 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 proteins which are found in many organisms, ranging from nematodes to human beings. They all have a very similar structure. 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.
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 domains of scaffold proteins.
=== 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 cysteines 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 | 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 = The Journal of Cell Biology | volume = 141 | issue = 7 | pages = 1539–1550 | date = June 1998 | pmid = 9647647 | pmc = 2132999 | 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 | 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 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
==Additional images== <gallery> File:TJschema.png File:Claudin.png File:Septatejunction.jpg File:Claudinhindgut.jpg </gallery>
== References == {{Reflist}}
{{Epithelial tissue}} {{Authority control}}
Category:Cell adhesion proteins Category:Structural proteins