Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. Tight junctions are important for the permeability properties of epithelial and endothelial barriers as they restrict diffusion along the paracellular space.

Function

 The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis.

The fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity.

In epithelial barrier, intercellular tight junctions provide a barrier to the back-diffusion of hydrogen ions. Epithelial disruption is followed rapidly by restitution, in which existing cells migrate along the exposed basement membrane to fill in the defects and restore epithelial barrier integrity.

 epithelial proliferation and differentiation

Tight junctions also function in the regulation of epithelial proliferation and differentiation. They harbour evolutionarily conserved protein complexes that regulate polarisation and junction assembly.

Tight junctions also recruit signalling proteins that participate in the regulation of cell proliferation and differentiation.

These signalling proteins include components that affect established signalling cascades and dual localisation proteins that can associate with junctions as well as travel to the nucleus where they regulate gene expression.

Structure

Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins (CLDNs), and JAMs have been recently discovered.

Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP.

Molecular components: claudins, occludins, JAMs

Pathology

 mutations in the claudin-1 gene (CLDN1) in neonatal ichthyosis-sclerosing cholangitis syndrome (607626)

 mutations in the claudin-14 gene (CLDN14) in hereditary deafness

 mutations in the claudin-16 gene (CLDN16) resultand hereditary hypomagnesemia.

 some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases.

 mutations of TJP2 (coding for tight junction protein 2) in familial hypercholanemia

 aberrant expression of tight junction-related proteins ZO-1, claudin-1 (CLD1) and occludin in synovial sarcoma (14704716)

See also

 apical junctions
 tight junction proteins
 claudins (CLDNs)

References

 Matter K, Aijaz S, Tsapara A, Balda MS. Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Curr Opin Cell Biol. 2005 Oct;17(5):453-8. PMID: 16098725

 Fasano A, Nataro JP. Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins. Adv Drug Deliv Rev. 2004 Apr 19;56(6):795-807. PMID: 15063590

 Van Itallie CM, Anderson JM. The molecular physiology of tight junction pores. Physiology (Bethesda). 2004 Dec;19:331-8. PMID: 15546850

 Liu Z, Li N, Neu J. Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr. 2005 Apr;94(4):386-93. PMID: 16092447

 Haynes MD, Martin TA, Jenkins SA, Kynaston HG, Matthews PN, Jiang WG. Tight junctions and bladder cancer. Int J Mol Med. 2005 Jul;16(1):3-9. PMID: 15942671

 Fasano A, Nataro JP. Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins. Adv Drug Deliv Rev. 2004 Apr 19;56(6):795-807. PMID: 15063590

 Sawada N, Murata M, Kikuchi K, Osanai M, Tobioka H, Kojima T, Chiba H. Tight junctions and human diseases. Med Electron Microsc. 2003 Sep;36(3):147-56. PMID: 14505058

 Gonzalez-Mariscal L, Betanzos A, Nava P, Jaramillo BE. Tight junction proteins. Prog Biophys Mol Biol. 2003 Jan;81(1):1-44. PMID: 12475568

 Huber JD, Egleton RD, Davis TP. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 2001 Dec;24(12):719-25. PMID: 11718877

 Lee DB, Huang E, Ward HJ. Tight junction biology and kidney dysfunction. Am J Physiol Renal Physiol. 2006 Jan;290(1):F20-34. PMID: 16339962

 Huber JD, Egleton RD, Davis TP. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 2001 Dec;24(12):719-25. PMID: 11718877

 Gasbarrini G, Montalto M. Structure and function of tight junctions. Role in intestinal barrier. Ital J Gastroenterol Hepatol. 1999 Aug-Sep;31(6):481-8. PMID: 10575567

 Hollander D. Clinician?s guide through the tight junctions. Ital J Gastroenterol Hepatol. 1999 Aug-Sep;31(6):435-9. PMID: 10575558

 Denker BM, Nigam SK. Molecular structure and assembly of the tight junction. Am J Physiol. 1998 Jan;274(1 Pt 2):F1-9. PMID: 9458817