title: Enterocyte loss of polarity and gut wound healing rely upon the F-actin-severing function of villin.
abstract: Efficient wound healing is required to maintain the integrity of the intestinal epithelial barrier because of its constant exposure to a large variety of environmental stresses. This process implies a partial cell depolarization and the acquisition of a motile phenotype that involves rearrangements of the actin cytoskeleton. Here we address how polarized enterocytes harboring actin-rich apical microvilli undergo extensive cell remodeling to drive injury repair. Using live imaging technologies, we demonstrate that enterocytes in vitro and in vivo rapidly depolarize their microvilli at the wound edge. Through its F-actin-severing activity, the microvillar actin-binding protein villin drives both apical microvilli disassembly in vitro and in vivo and promotes lamellipodial extension. Photoactivation experiments indicate that microvillar actin is mobilized at the lamellipodium, allowing optimal migration. Finally, efficient repair of colonic mechanical injuries requires villin severing of F-actin, emphasizing the importance of villin function in intestinal homeostasis. Thus, villin severs F-actin to ensure microvillus depolarization and enterocyte remodeling upon injury. This work highlights the importance of specialized apical pole disassembly for the repolarization of epithelial cells initiating migration.
authors.affiliation: Unité Mixte de Recherche 144, Centre National de la Recherche Scientifique, Institut Curie, 75248 Paris Cedex 05, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Ubelmann
authors.forename: Mathias
authors.initials: M
authors.lastname: Chamaillard
authors.forename: Fatima
authors.initials: F
authors.lastname: El-Marjou
authors.forename: Anthony
authors.initials: A
authors.lastname: Simon
authors.forename: Jeanne
authors.initials: J
authors.lastname: Netter
authors.forename: Danijela
authors.initials: D
authors.lastname: Vignjevic
authors.forename: Buford L
authors.initials: BL
authors.lastname: Nichols
authors.forename: Roberto
authors.initials: R
authors.lastname: Quezada-Calvillo
authors.forename: Teddy
authors.initials: T
authors.lastname: Grandjean
authors.forename: Daniel
authors.initials: D
authors.lastname: Louvard
authors.forename: Céline
authors.initials: C
authors.lastname: Revenu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D004724:Endoscopy; D020895:Enterocytes / Q000166:cytology* / Q000378:metabolism; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D008871:Microvilli / Q000378:metabolism; D010641:Phenotype; D013552:Swine; D014945:Wound Healing
chemical_list: D000199:Actins; D008840:Microfilament Proteins; C026615:villin