Claudins are a family of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s which, along with

occludin Occludin is an enzyme ( EC 1.6) that oxidizes NADH. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with Claudins, and zonula occludens-1 (ZO-1), occludin has bee ...

, are the most important components of the

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

s ( zonulae occludentes). Tight junctions establish the

paracellular Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space ''between'' the cells. It is in contrast to transcellular transport, where the substances travel ''through'' the cell, pass ...

barrier that controls the flow of molecules in the intercellular space between the cells of an

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

. 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 ami ...

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) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...

(kDa))

transmembrane protein A transmembrane protein (TP) 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 frequentl ...

s which are found in many

organisms In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fungi; ...

, ranging from

nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...

s to

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

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, 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 the protein is ...

both located in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

, 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-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to ...

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) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bil ...

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 formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

s of found on the first extracellular loop form

disulfide bonds In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. 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 is three hydrophobic resides. 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 , mottoeng = Freedom of academic culture , established = , type = National university, Public (National) , endowment = ¥ 316 billion (2.4 1000000000 (number), billion USD) , faculty = 3,480 (Teaching Staff) , administrative_staff ...

. The name ''claudin'' comes from

Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...

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 parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...

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 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 seals ...

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 physiolo ...

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, form ...

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 of ...

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 str ...

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 occlude ...

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 occlude ...

CLDN8 Claudin-8 is a protein that in humans is encoded by the ''CLDN8'' gene. It belongs to the group of claudins. References External links * Further reading

* * * * * * * * * * * * * * * {{gene-21-stub ...

CLDN9 Claudin-9 is a protein that in humans is encoded by the ''CLDN9'' 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 occlude ...

CLDN10 Claudin-10 is a protein that in humans is encoded by the ''CLDN10'' 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 occlud ...

CLDN11 Claudin-11 is a protein that in humans is encoded by the ''CLDN11'' 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 occlud ...

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 occlu ...

, 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 ce ...

CLDN15 Claudin-15 is a protein that in humans is encoded by the ''CLDN15'' gene. It belongs to the group of claudins. Among its related pathways are Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways Signal transduct ...

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 Tight junctions, also known as occluding junctions ...

CLDN19 Claudin-19 is a protein that in humans is encoded by the ''CLDN19'' 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 ...

CLDN20 Claudin-20 is a protein that in humans is encoded by the ''CLDN20'' 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 occlud ...

, CLDN21,

CLDN22 Claudin-22 is a protein that in humans is encoded by the ''CLDN22'' 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 ...

, CLDN23

Additional images

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

References

{{Epithelial tissue Cell adhesion proteins Structural proteins fr:Jonction serrée#Claudines