Claudins are a family of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s which, along with

occludin Occludin is a transmembrane protein that regulates the permeability of epithelial and endothelial barriers. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with ...

, are the most important components of the

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...

s ( zonulae occludentes). Tight junctions establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

. They have four transmembrane domains, with the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

and the C-terminus in the cytoplasm.

Structure

Claudins are small (20–24/27

kilodalton The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

(kDa))

transmembrane protein A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...

s which are found in many

organisms An organism is any living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have been pr ...

, ranging from

nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...

s to

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

beings. They all have a very similar structure. Claudins span the cellular membrane 4 times, with the

N-terminal end The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

and the

C-terminal end The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When ...

both located in the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

, and two extracellular loops which show the highest degree of conservation. Claudins have both cis and trans interactions between cell membranes. Cis-interactions is when claudins on the same membrane interact, one way they interact is by transmembrane domain having molecular interactions. Trans-interaction is when claudins of neighboring cells interact through their extracellular loops. Cis-interactions is also known as side-to-side interactions and trans-interactions is also known as head-to-head interactions. 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.

N-terminal

The N-terminal end is usually very short (1–10 amino acids) It is located in the cytoplasm where it is thought to help to contribute to cell signaling, cytoskeletal organization and other possible functions.

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. It is thought that it may play a role in cell signaling. All human claudins (with the exception of Claudin 12) have domains that let them bind to

PDZ domain The PDZ domain is a common structural domain of 80-90 Amino acid, amino-acids found in the Signal transduction, signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring recept ...

s of

scaffold protein In biology, scaffold proteins are crucial regulators of many key signalling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signalling pathway, tethering them in ...

Transmembrane domain

The

transmembrane domain A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...

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 Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

s of found on the first extracellular loop form

disulfide bonds In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In in ...

. 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.

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.

History

Claudins were first named in 1998 by Japanese researchers Mikio Furuse and Shoichiro Tsukita at

Kyoto University , or , is a National university, national research university in Kyoto, Japan. Founded in 1897, it is one of the former Imperial Universities and the second oldest university in Japan. The university has ten undergraduate faculties, eighteen gra ...

. The name ''claudin'' comes from

Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...

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 Proteomics is the large-scale study of proteins. Proteins are vital macromolecules of all living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replicatio ...

techniques. A chimeric claudin was synthesized to help enhance the understanding of both the structure and function of the tight junction. Computational modeling is also another technique being used to help enhance research into the structure and functions of claudins.

Genes

There are 23 genes found in the human genome for claudin proteins and there are 27 transmembrane domains across mammals. 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 Claudin-1 is a protein that in humans is encoded by the ''CLDN1'' gene. It belongs to the group of claudins. Function Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seal ...

'', ''

CLDN2 Claudin-2 is a protein that in humans is encoded by the ''CLDN2'' gene. It belongs to the group of claudins. Members of the claudin protein family, such as CLDN2, are expressed in an organ-specific manner and regulate the tissue-specific physiol ...

'', ''

CLDN3 Claudin 3, also known as CLDN3, is a protein which in humans is encoded by the ''CLDN3'' gene. It is a member of the claudin protein family. Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, for ...

'', ''

CLDN4 Claudin 4, also known as CLDN4, is a protein which in humans is encoded by the ''CLDN4'' gene. It belongs to the group of claudins. This gene encodes an integral membrane protein, which belongs to the claudin family. The protein is a component o ...

'', ''

CLDN5 Claudin-5 is a protein that in humans is encoded by the ''CLDN5'' gene. It belongs to the group of claudins. Function This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction s ...

'', ''

CLDN6 Claudin-6 is a protein that in humans is encoded by the ''CLDN6'' gene. It belongs to the group of claudin Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occlu ...

'', ''

CLDN7 Claudin-7 is a protein that in humans is encoded by the ''CLDN7'' gene. It belongs to the group of claudin Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occl ...

'', ''

CLDN8 Claudin-8 is a protein that in humans is encoded by the ''CLDN8'' gene. It belongs to the group of claudin Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occlu ...

'', '' CLDN9'', '' CLDN10'', '' CLDN11'', ''

CLDN12 Claudin-12 is a protein that in humans is encoded by the ''CLDN12'' gene. It belongs to the group of claudin Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occ ...

'', '' CLDN13'', ''

CLDN14 Claudin-14 is a protein that in humans is encoded by the ''CLDN14'' gene. It belongs to a related family of proteins called claudins. The protein encoded by CLDN14 is an integral membrane protein and a component of tight junctions, one mode of c ...

'', '' CLDN15'', ''

CLDN16 Claudin-16 is a protein that in humans is encoded by the ''CLDN16'' gene. It belongs to the group of claudins. Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around c ...

'', '' CLDN17'', ''

CLDN18 Claudin-18 is a protein that in humans is encoded by the ''CLDN18'' gene. It belongs to the group of claudins. CLDN18 belongs to the large claudin family of proteins, which form tight junction strands in epithelial cells . upplied by OMIMref nam ...

'', ''

CLDN19 Claudin-19 is a protein that in humans is encoded by the ''CLDN19'' gene. It belongs to the group of claudins. Claudin-19 has been implicated in Magnesium transporter#Paracellular transport, magnesium transport. Claudins, such as CLDN19, are tra ...

'', '' CLDN20'', '' CLDN21'', '' CLDN22'', '' CLDN23''

Additional images

File:TJschema.png File:Claudin.png File:Septatejunction.jpg File:Claudinhindgut.jpg

References

{{Authority control Cell adhesion proteins Structural proteins fr:Jonction serrée#Claudines

Structure

N-terminal

C-terminal

Transmembrane domain

First extracellular loop

Second extracellular loop

History

Studies

Genes

See also

Additional images

References