Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo.
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.
Marchiando
Amanda M
AM
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
Shen
Le
L
Graham
W Vallen
WV
Weber
Christopher R
CR
Schwarz
Brad T
BT
Austin
Jotham R
JR
Raleigh
David R
DR
Guan
Yanfang
Y
Watson
Alastair J M
AJ
Montrose
Marshall H
MH
Turner
Jerrold R
JR
D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D062793:Occludin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
D051242:Caveolin 1; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein