title: Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo.
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.
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Marchiando
authors.forename: Le
authors.initials: L
authors.lastname: Shen
authors.forename: W Vallen
authors.initials: WV
authors.lastname: Graham
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Weber
authors.forename: Brad T
authors.initials: BT
authors.lastname: Schwarz
authors.forename: Jotham R
authors.initials: JR
authors.lastname: Austin
authors.forename: David R
authors.initials: DR
authors.lastname: Raleigh
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Guan
authors.forename: Alastair J M
authors.initials: AJ
authors.lastname: Watson
authors.forename: Marshall H
authors.initials: MH
authors.lastname: Montrose
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
mesh_terms: 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
chemical_list: 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