The claudins.
The claudin multigene family encodes tetraspan membrane proteins that are crucial structural and functional components of tight junctions, which have important roles in regulating paracellular permeability and maintaining cell polarity in epithelial and endothelial cell sheets. In mammals, the claudin family consists of 24 members, which exhibit complex tissue-specific patterns of expression. The extracellular loops of claudins from adjacent cells interact with each other to seal the cellular sheet and regulate paracellular transport between the luminal and basolateral spaces. The claudins interact with multiple proteins and are intimately involved in signal transduction to and from the tight junction. Several claudin mouse knockout models have been generated and the diversity of phenotypes observed clearly demonstrates their important roles in the maintenance of tissue integrity in various organs. In addition, mutation of some claudin genes has been causatively associated with human diseases and claudin genes have been found to be deregulated in various cancers. The mechanisms of claudin regulation and their exact roles in normal physiology and disease are being elucidated, but much work remains to be done. The next several years are likely to witness an explosion in our understanding of these proteins, which may, in turn, provide new approaches for the targeted therapy of various diseases.
Lal-Nag
Madhu
M
Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, National Institutes of Health Biomedical Research Center, MD 21224, USA.
Morin
Patrice J
PJ
D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D019108:Tight Junctions / Q000737:chemistry
D008565:Membrane Proteins
Protein Sci. 2003 Feb;12(2):218-27
12538885
Genome Res. 2004 Jul;14(7):1248-57
15197168
Cancer Res. 2005 Aug 15;65(16):7378-85
16103090
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4690-4
15070779
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):511-6
9892664
Breast Cancer Res. 2005;7(2):R248-55
15743505
J Clin Invest. 2008 Feb;118(2):619-28
18188451
J Cell Biol. 1998 Jun 29;141(7):1539-50
9647647
J Biol Chem. 2007 Oct 12;282(41):30005-13
17699514
J Biol Chem. 2002 Jul 26;277(30):27501-9
12021270
Am J Hum Genet. 2006 Nov;79(5):949-57
17033971
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10196-201
11517306
Biochim Biophys Acta. 2008 Mar;1778(3):631-45
18036336
IUBMB Life. 2009 Apr;61(4):431-7
19319969
J Biol Chem. 2002 Jan 4;277(1):455-61
11689568
Cancer Res. 2005 Nov 1;65(21):9603-6
16266975
J Cell Physiol. 2005 Apr;203(1):15-26
15389642
Nat Rev Mol Cell Biol. 2001 Apr;2(4):285-93
11283726
Gastroenterology. 2004 Nov;127(5):1386-90
15521008
J Cell Biol. 2000 Apr 3;149(1):13-6
10747082
J Biol Chem. 2005 Jul 15;280(28):26233-40
15905176
Biochim Biophys Acta. 2008 Mar;1778(3):729-56
17950242
J Virol. 2007 Nov;81(22):12465-71
17804490
J Biol Chem. 2004 Jan 30;279(5):3543-52
14593119
Hum Genet. 2000 Sep;107(3):249-56
11071387
Eur J Cell Biol. 2004 May;83(4):135-44
15260435
J Cell Sci. 2004 Mar 1;117(Pt 7):1247-57
14996944
J Cell Sci. 2005 Apr 1;118(Pt 7):1427-36
15769849
J Cell Sci. 2003 May 15;116(Pt 10):1959-67
12668723
J Cell Biol. 2002 Mar 18;156(6):1099-111
11889141
J Cell Biol. 2005 May 9;169(3):527-38
15883201
FASEB J. 2008 Jan;22(1):146-58
17761522
J Cell Biol. 2004 Jan 19;164(2):313-23
14734539
J Biol Chem. 1997 Oct 17;272(42):26652-8
9334247
Annu Rev Physiol. 2006;68:403-29
16460278
Hum Mol Genet. 2003 Aug 15;12(16):2049-61
12913076
Nature. 2007 Apr 12;446(7137):801-5
17325668
Mod Pathol. 2005 Apr;18(4):511-8
15475928
J Neurosci. 2004 Aug 11;24(32):7051-62
15306639
BMC Cancer. 2006 Jul 12;6:186
16836752
J Cell Sci. 2004 Oct 1;117(Pt 21):5087-96
15456848
J Cell Biol. 1999 Dec 13;147(6):1351-63
10601346
Cell. 2001 Jan 12;104(1):165-72
11163249
Science. 1999 Jul 2;285(5424):103-6
10390358
Am J Physiol Renal Physiol. 2008 Oct;295(4):F867-76
18480174
Am J Physiol Cell Physiol. 2002 Jul;283(1):C142-7
12055082
Exp Cell Res. 2007 Sep 10;313(15):3364-75
17678893