Dynamic regulation of epithelial cell fate and barrier function by intercellular junctions.

Abstract:

:In the intestine, a single layer of epithelial cells effectively separates potentially harmful luminal content from the underlying tissue. The importance of an intact mucosal layer is highlighted by pathological disorders of the gut such as inflammatory bowel disease, in which disruption of the epithelial barrier leads to severe inflammation of the submucosal tissue compartments. Epithelial barrier function is provided by tightly regulated intercellular junctions, which consist of a plethora of membrane-associated and transmembrane proteins organized in discreet, spatially restricted complexes. Classically, these complexes are known to be dynamic seals for fluids and small molecules, as well as to provide mechanical strength by anchoring cell-cell contacts to the cytoskeleton. Rather than just acting as simple gates and adapters, however, junctional complexes themselves can relay extracellular stimuli to the epithelium and initiate cellular responses such as differentiation and apoptosis. In this review, we will highlight recent studies by our group and others which discuss how junctional proteins can promote outside-to-inside signaling and modulate epithelial cell fate. Unraveling the complex crosstalk between epithelial cells and their intercellular junctions is essential to understanding how epithelial barrier function is maintained in vivo and might provide new strategies for the treatment of inflammatory disorders of the intestine.

journal_name

Ann N Y Acad Sci

authors

Koch S,Nusrat A

doi

10.1111/j.1749-6632.2009.04025.x

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

220-7

eissn

0077-8923

issn

1749-6632

pii

NYAS04025

journal_volume

1165

pub_type

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