CLDN4 explained

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 tight junction strands and may play a role in internal organ development and function during pre- and postnatal life. This gene is deleted in Williams-Beuren syndrome, a neurodevelopmental disorder affecting multiple systems.^[1]

Claudin 4 can also be used as a marker for distinguishing malignant mesothelioma from lung cancer and uterine serous carcinoma.^[2] As a pancreatic cancer marker in cell-blocks of effusion specimens, it has also been found to have a superior performance to BerEp4 staining.^[3]

Further reading

• Kniesel U, Wolburg H . Tight junctions of the blood–brain barrier. . Cell. Mol. Neurobiol. . 20 . 1 . 57–76 . 2000 . 10690502 . 10.1023/A:1006995910836 . 26473781 .
• Heiskala M, Peterson PA, Yang Y . The roles of claudin superfamily proteins in paracellular transport. . Traffic . 2 . 2 . 93–8 . 2001 . 11247307 . 10.1034/j.1600-0854.2001.020203.x . 12132159 .
• Tsukita S, Furuse M, Itoh M . Multifunctional strands in tight junctions. . Nat. Rev. Mol. Cell Biol. . 2 . 4 . 285–93 . 2001 . 11283726 . 10.1038/35067088 . 36524601 .
• Tsukita S, Furuse M . Claudin-based barrier in simple and stratified cellular sheets. . Curr. Opin. Cell Biol. . 14 . 5 . 531–6 . 2003 . 12231346 . 10.1016/S0955-0674(02)00362-9 .
• González-Mariscal L, Betanzos A, Nava P, Jaramillo BE . Tight junction proteins. . Prog. Biophys. Mol. Biol. . 81 . 1 . 1–44 . 2003 . 12475568 . 10.1016/S0079-6107(02)00037-8 .
• Katahira J, Inoue N, Horiguchi Y . Molecular cloning and functional characterization of the receptor for Clostridium perfringens enterotoxin. . J. Cell Biol. . 136 . 6 . 1239–47 . 1997 . 9087440 . 10.1083/jcb.136.6.1239 . 2132509 . etal.
• Katahira J, Sugiyama H, Inoue N . Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. . J. Biol. Chem. . 272 . 42 . 26652–8 . 1997 . 9334247 . 10.1074/jbc.272.42.26652 . etal. free.
• Paperna T, Peoples R, Wang YK . Genes for the CPE receptor (CPETR1) and the human homolog of RVP1 (CPETR2) are localized within the Williams-Beuren syndrome deletion. . Genomics . 54 . 3 . 453–9 . 1999 . 9878248 . 10.1006/geno.1998.5619 . etal. free .
• Morita K, Furuse M, Fujimoto K, Tsukita S . Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 2 . 511–6 . 1999 . 9892664 . 10.1073/pnas.96.2.511 . 15167 . 1999PNAS...96..511M . free .
• Itoh M, Furuse M, Morita K . Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. . J. Cell Biol. . 147 . 6 . 1351–63 . 2000 . 10601346 . 10.1083/jcb.147.6.1351 . 2168087 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Colegio OR, Van Itallie C, Rahner C, Anderson JM . Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture. . Am. J. Physiol., Cell Physiol. . 284 . 6 . C1346–54 . 2003 . 12700140 . 10.1152/ajpcell.00547.2002 .
• Katoh M, Katoh M . CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. . Int. J. Mol. Med. . 11 . 6 . 683–9 . 2004 . 12736707 . 10.3892/ijmm.11.6.683.
• Hillier LW, Fulton RS, Fulton LA . The DNA sequence of human chromosome 7. . Nature . 424 . 6945 . 157–64 . 2003 . 12853948 . 10.1038/nature01782 . 2003Natur.424..157H . etal. free .
• Michl P, Barth C, Buchholz M . Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. . Cancer Res. . 63 . 19 . 6265–71 . 2003 . 14559813 . etal.
• Liu F, Koval M, Ranganathan S, Fanayan S, Hancock WS, Lundberg EK, Beavis RC, Lane L, Duek P, McQuade L, Kelleher NL, Baker MS . A systems proteomics view of the endogenous human claudin protein family . J Proteome Res . 15 . 2 . 339–59 . 2015 . 26680015 . 4777318 . 10.1021/acs.jproteome.5b00769 .
• Ohta Y, Sasaki Y, Saito M, Kushima M, Takimoto M, Shiokawa A, Ota H . Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma . Int J Surg Pathol . 21 . 5 . 493–501 . 2013 . 23775021 . 10.1177/1066896913491320 . 6840615 .
• Vojtek M, Walsh MD, Papadimos DJ, Shield PW . Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens . Cytopathology . 30 . 6 . 614–619 . 2019 . 10.1111/cyt.12765 . 31390089 . 199468828 .

Notes and References

1. Web site: Entrez Gene: CLDN4 claudin 4.
2. Ohta Y, Sasaki Y, Saito M, Kushima M, Takimoto M, Shiokawa A, Ota H . Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma . Int J Surg Pathol . 21 . 5 . 493–501 . 2013 . 23775021 . 10.1177/1066896913491320 . 6840615 .
3. Vojtek M, Walsh MD, Papadimos DJ, Shield PW . Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens . Cytopathology . 30 . 6 . 614–619 . 2019 . 10.1111/cyt.12765 . 31390089 . 199468828 .