Claudin

Structure

Claudins are small (20–24/27 kilodalton (kDa)) 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. 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 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.

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. 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.

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, CLDN2, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CLDN10, CLDN11, CLDN12, CLDN13, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN20, CLDN21, CLDN22, CLDN23

Additional images

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

References

fr:Jonction serrée#Claudines

References

1. (2010-01-01). "Current Topics in Membranes". Academic Press.
2. (2010-01-01). "Current Topics in Membranes". Academic Press.
3. (2014-01-01). "International Review of Cell and Molecular Biology". Academic Press.
4. (October 2019). "Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity". The Journal of Cell Biology.
5. (2019-01-01). "Nervous System Drug Delivery". Academic Press.
6. (2010-01-01). "Current Topics in Membranes". Academic Press.
7. (April 2013). "Claudins and the modulation of tight junction permeability". Physiological Reviews.
8. (September 2010). "Crystal Structures of claudins: insights into their intermolecular interactions". Annals of the New York Academy of Sciences.
9. (January 2020). "Computational Modeling of Claudin Structure and Function". International Journal of Molecular Sciences.
10. (February 2019). "The Claudins: From Tight Junctions to Biological Systems". Trends in Biochemical Sciences.
11. (May 2004). "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". European Journal of Cell Biology.
12. (May 2021). "Chimeric Claudins: A New Tool to Study Tight Junction Structure and Function". International Journal of Molecular Sciences.
13. (2019-01-01). "The Paracellular Channel". Academic Press.
14. (2019-01-01). "The Paracellular Channel". Academic Press.