A central role for vimentin in regulating repair function during healing of the lens epithelium.
Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 Wills Vision Research Center at Jefferson, Philadelphia, PA 19107 Department of Anatomy and Regenerative Biology, George Washington University, Washington, DC 20037.
A S
AS
Menko
B M
BM
Bleaken
A A
AA
Libowitz
L
L
Zhang
M A
MA
Stepp
J L
JL
Walker
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D002642:Chick Embryo; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D022001:Focal Adhesions / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism / Q000648:ultrastructure; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D054358:Withanolides / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
D000199:Actins; D051419:Paxillin; D034741:RNA, Small Interfering; D014746:Vimentin; D054358:Withanolides; D009218:Myosins; C009684:withaferin A