A central role for vimentin in regulating repair function during healing of the lens epithelium

• Published in: Molecular biology of the cell Vol. 25; no. 6; pp. 776 - 790
• Main Authors: Menko, A S, Bleaken, B M, Libowitz, A A, Zhang, L, Stepp, M A, Walker, J L
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.03.2014
• Series: A Highlights from
• Subjects: Actins - genetics; Actins - metabolism; Animals; Cell Movement; Chick Embryo; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - ultrastructure; Epithelium - metabolism; Epithelium - ultrastructure; Focal Adhesions - metabolism; Focal Adhesions - ultrastructure; Gene Expression Regulation; Humans; Intermediate Filaments - metabolism; Intermediate Filaments - ultrastructure; Lens, Crystalline - cytology; Lens, Crystalline - drug effects; Lens, Crystalline - metabolism; Lens, Crystalline - surgery; Microtubules - metabolism; Microtubules - ultrastructure; Myosins - genetics; Myosins - metabolism; Paxillin - genetics; Paxillin - metabolism; Pseudopodia - metabolism; Pseudopodia - ultrastructure; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Vimentin - antagonists & inhibitors; Vimentin - genetics; Vimentin - metabolism; Withanolides - pharmacology; Wound Healing - drug effects; Wound Healing - genetics
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.e12-12-0900

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.