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PMID: 20351069 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo.

The Journal of cell biology ·Vol. 189 ·No. 1 ·2010-04-05 ·Pages 111-26

Marchiando AM, Shen L, Graham WV, Weber CR, Schwarz BT, Austin JR, Raleigh DR, Guan Y, Watson AJ, Montrose MH, Turner JR

Abstract

Epithelial paracellular barrier function, determined primarily by tight junction permeability, is frequently disrupted in disease. In the intestine, barrier loss can be mediated by tumor necrosis factor (alpha) (TNF) signaling and epithelial myosin light chain kinase (MLCK) activation. However, TNF induces only limited alteration of tight junction morphology, and the events that couple structural reorganization to barrier regulation have not been defined. We have used in vivo imaging and transgenic mice expressing fluorescent-tagged occludin and ZO-1 fusion proteins to link occludin endocytosis to TNF-induced tight junction regulation. This endocytosis requires caveolin-1 and is essential for structural and functional tight junction regulation. These data demonstrate that MLCK activation triggers caveolin-1-dependent endocytosis of occludin to effect structural and functional tight junction regulation.

MeSH Terms
Animals Caveolin 1/genetics,metabolism Endocytosis/physiology Membrane Proteins/genetics,metabolism Mice Mice, Transgenic Occludin Phosphoproteins/genetics,metabolism Signal Transduction Tight Junctions/metabolism Tumor Necrosis Factor-alpha/metabolism Zonula Occludens-1 Protein
Chemicals
Caveolin 1 Membrane Proteins Occludin Ocln protein, mouse Phosphoproteins Tjp1 protein, mouse Tumor Necrosis Factor-alpha Zonula Occludens-1 Protein
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Marchiando Amanda M
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
Shen Le
Graham W Vallen
Weber Christopher R
Schwarz Brad T
Austin Jotham R
Raleigh David R
Guan Yanfang
Watson Alastair J M
Montrose Marshall H
Turner Jerrold R
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200902153
Published
2010-04-05
Epub
2010-00-29
Pages
111-26
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2854371
Subset
IM
Grants
NIDDK NIH HHS · P01 DK067887 · United States
NCI NIH HHS · P30CA14599 · United States
NCRR NIH HHS · UL1 RR024999 · United States
NCI NIH HHS · P30 CA014599 · United States
NIDDK NIH HHS · R21 DK074976 · United States
NHLBI NIH HHS · T32 HL007237 · United States
NIDDK NIH HHS · R01 DK061931 · United States
NIDDK NIH HHS · R01 DK068271 · United States
NIDDK NIH HHS · R01DK61931 · United States
NCRR NIH HHS · UL1RR024999 · United States
NHLBI NIH HHS · T32HL007237 · United States
NIDDK NIH HHS · P01DK67887 · United States
NIDDK NIH HHS · R01DK68271 · United States
External Links
PubMed source DOI: 10.1083/jcb.200902153 PMC Full Text View journal details
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