Claudins are a family ofproteins which, along withoccludin, are the most important components of thetight junctions (zonulae occludentes).[1][2] Tight junctions establish theparacellular barrier that controls the flow of molecules in the intercellular space between the cells of anepithelium.[1][3][4] They have four transmembrane domains, with theN-terminus and the C-terminus in the cytoplasm.
Claudins have both cis and trans interactions between cell membranes.[6] Cis-interactions is when claudins on the same membrane interact, one way they interact is by transmembrane domain having molecular interactions.[7] Trans-interaction is when claudins of neighboring cells interact through their extracellular loops.[8] Cis-interactions is also known as side-to-side interactions and trans-interactions is also known as head-to-head interactions.[9]
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.[7]
The N-terminal end is usually very short (1–10 amino acids)[10][8] It is located in the cytoplasm where it is thought to help to contribute to cell signaling, cytoskeletal organization and other possible functions.[11]
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.[10] It is thought that it may play a role in cell signaling.[11] All human claudins (with the exception of Claudin 12) have domains that let them bind toPDZ domains ofscaffold proteins.
The first extracellular loop has a range of 42-56 amino acids and is longer than the second extracellular loop. It is suspected that thecysteines of found on the first extracellular loop formdisulfide 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.[7]
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.[7]
Claudins were first named in 1998 by Japanese researchers Mikio Furuse and Shoichiro Tsukita atKyoto University.[12] The nameclaudin comes fromLatin wordclaudere ("to close"), suggesting the barrier role of these proteins.
A recent review discusses evidence regarding the structure and function of claudin family proteins using a systems approach to understand evidence generated byproteomics techniques.[13]
A chimeric claudin was synthesized to help enhance the understanding of both the structure and function of the tight junction.[14]
Computational modeling is also another technique being used to help enhance research into the structure and functions of claudins.[9]
There are 23 genes found in the human genome for claudin proteins[14] and there are 27 transmembrane domains across mammals.[8][11] The conservation is not observed on agenetic level. Despite the genetic level not being conserved across claudins their structural conservation are very similar.
^abHou J, Konrad M (2010-01-01). "Chapter 7 - Claudins and Renal Magnesium Handling". In Yu AS (ed.).Current Topics in Membranes. Vol. 65. Academic Press. pp. 151–176.doi:10.1016/s1063-5823(10)65007-7.ISBN9780123810397.
^Furuse M (2010-01-01). "Chapter 1 - Introduction: Claudins, Tight Junctions, and the Paracellular Barrier". In Yu AS (ed.).Current Topics in Membranes. Vol. 65. Academic Press. pp. 1–19.doi:10.1016/s1063-5823(10)65001-6.ISBN9780123810397.
^Szaszi K, Amoozadeh Y (2014-01-01). "Chapter Six - New Insights into Functions, Regulation, and Pathological Roles of Tight Junctions in Kidney Tubular Epithelium". In Jeon KW (ed.).International Review of Cell and Molecular Biology. Vol. 308. Academic Press. pp. 205–271.doi:10.1016/b978-0-12-800097-7.00006-3.ISBN9780128000977.PMID24411173.
^Haseloff RF, Piontek J, Blasig IE (2010-01-01). "Chapter 5 - The Investigation of cis- and trans-Interactions Between Claudins". In Yu AS (ed.).Current Topics in Membranes. Vol. 65. Academic Press. pp. 97–112.doi:10.1016/s1063-5823(10)65005-3.ISBN9780123810397.
^abRüffer C, Gerke V (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.83 (4):135–144.doi:10.1078/0171-9335-00366.PMID15260435.
