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Claudins and Other Tight Junction Proteins

  1. Dorothee Günzel,
  2. Michael Fromm

Published Online: 1 JUL 2012

DOI: 10.1002/cphy.c110045

Comprehensive Physiology

Comprehensive Physiology

How to Cite

Günzel, D. and Fromm, M. 2012. Claudins and Other Tight Junction Proteins. Comprehensive Physiology. 2:1819–1852.

Author Information

  1. Institute of Clinical Physiology, Charité, Universtätsmedizin Berlin, Campus Benjamin Franklin, Freie Universität/Humboldt-Universität, Berlin, Germany

Publication History

  1. Published Online: 1 JUL 2012

Abstract

Epithelial transport relies on the proper function and regulation of the tight junction (TJ), other-wise uncontrolled paracellular leakage of solutes and water would occur. They also act as a fence against mixing of membrane proteins of the apical and basolateral side. The proteins determining paracellular transport consist of four transmembrane regions, intracellular N and C terminals, one intracellular and two extracellular loops (ECLs). The ECLs interact laterally and with counterparts of the neighboring cell and by this achieve a general sealing function. Two TJ protein families can be distinguished, claudins, comprising 27 members in mammals, and TJ-associated MARVEL proteins (TAMP), comprising occludin, tricellulin, and MarvelD3. They are linked to a multitude of TJ-associated regulatory and scaffolding proteins. The major TJ proteins are classified according to the physiological role they play in enabling or preventing paracellular transport. Many TJ proteins have sealing functions (claudins 1, 3, 5, 11, 14, 19, and tricellulin). In contrast, a significant number of claudins form channels across TJs which feature selectivity for cations (claudins 2, 10b, and 15), anions (claudin-10a and -17), or are permeable to water (claudin-2). For several TJ proteins, function is yet unclear as their effects on epithelial barriers are inconsistent (claudins 4, 7, 8, 16, and occludin). TJs undergo physiological and pathophysiological regulation by altering protein composition or abundance. Major pathophysiological conditions which involve changes in TJ protein composition are (1) effects of pathogens binding to TJ proteins, (2) altered TJ protein composition during inflammation and infection, and (3) altered TJ protein expression in cancers. © 2012 American Physiological Society. Compr Physiol 2:1819-1852, 2012.