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J Biol Chem, Vol. 275, Issue 8, 5773-5778, February 25, 2000
From the Département de Biologie Cellulaire, Université
de Genève, Sciences III, 30 Quai Ernest-Ansermet,
1211 Genève-4, Switzerland
Neutrophils cross epithelial sheets to reach
inflamed mucosal surfaces by migrating along the paracellular route. To
avoid breakdown of the epithelial barrier, this process requires
coordinated opening and closing of tight junctions, the most apical
intercellular junctions in epithelia. To determine the function of
epithelial tight junction proteins in this process, we analyzed
neutrophil migration across monolayers formed by stably transfected
epithelial cells expressing wild-type and mutant occludin, a membrane
protein of tight junctions with four transmembrane domains and both
termini in the cytosol. We found that expression of mutants with a
modified N-terminal cytoplasmic domain up-regulated migration, whereas deletion of the C-terminal cytoplasmic domain did not have an effect.
The N-terminal cytosolic domain was also found to be important for the
linear arrangement of occludin within tight junctions but not for the
permeability barrier. Moreover, expression of mutant occludin bearing a
mutation in one of the two extracellular domains inhibited neutrophil
migration. The effects of transfected occludin mutants on neutrophil
migration did not correlate with their effects on selective
paracellular permeability and transepithelial electrical resistance.
Hence, specific domains and functional properties of occludin modulate
transepithelial migration of neutrophils.
Occludin Modulates Transepithelial Migration of Neutrophils*
,
*
The research in the authors' laboratory was supported by
the Wolfermann-Nägeli Stiftung, the Helmut Horton Stiftung, the Novartis Stiftung, the Swiss National Science Foundation, and the
Canton de Genève.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Current address: Dept. of Clinical Biochemistry, University of
Geneva, Geneva, Switzerland.
§
A fellow of the Swiss Talents in Academic Research and Teaching
program of the Swiss National Science Foundation. To whom correspondence should be addressed. Tel.: 41-22-702-6729; Fax: 41-22-781-1747; E-mail:
Matter@cellbio.unige.ch.
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