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Am J Physiol Cell Physiol 286: C1213-C1228, 2004; doi:10.1152/ajpcell.00558.2003
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INVITED REVIEW

The tight junction: a multifunctional complex

Eveline E. Schneeberger1 and Robert D. Lynch2

1Molecular Pathology Unit, Massachusetts General Hospital, Charlestown 02129; and 2Biological Sciences, University of Massachusetts at Lowell, Lowell, Massachusetts 01854

Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins—occludin, claudins, and junction adhesion molecules—interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity.

tight junction structure; function; regulation



Address for reprint requests and other correspondence: E. E. Schneeberger, Molecular Pathology Unit, 149-7151, Massachusetts General Hospital East, 149 13th St., Charlestown, MA 02129 (E-mail: eschneeberger{at}partners.org).




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