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New Philadelphia, PA, United States

Menko A.S.,Thomas Jefferson University | Menko A.S.,Wills Vision Research Center at Jefferson | Bleaken B.M.,Thomas Jefferson University | Libowitz A.A.,Thomas Jefferson University | And 5 more authors.
Molecular Biology of the Cell | Year: 2014

Mock cataract surgery provides a unique ex vivo model for studying wound re pair 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 pre dominant 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 lamel lipodial 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 vimen tin 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 myo sin 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. © 2014 Menko et al. Source

Menko A.S.,Thomas Jefferson University | Menko A.S.,Wills Vision Research Center at Jefferson | Bleaken B.M.,Thomas Jefferson University | Walker J.L.,Thomas Jefferson University | Walker J.L.,Wills Vision Research Center at Jefferson
Experimental Cell Research | Year: 2014

This study investigates how epithelial cells moving together function to coordinate their collective movement to repair a wound. Using a lens ex vivo mock cataract surgery model we show that region-specific reorganization of cell-cell junctions, cytoskeletal networks and myosin function along apical and basal domains of an epithelium mediates the process of collective migration. An apical junctional complex composed of N-cadherin/ZO-1/myosin II linked to a cortical actin cytoskeleton network maintains integrity of the tissue during the healing process. These cells' basal domains often preceded their apical domains in the direction of movement, where an atypical N-cadherin/ZO-1 junction, linked to an actin stress fiber network rich in phosphomyosin, was prominent in cryptic lamellipodia. These junctions joined the protruding forward-moving lamellipodia to the back end of the cell moving directly in front of it. These were the only junctions detected in cryptic lamellipodia of lens epithelia migrating in response to wounding that could transmit the protrusive forces that drive collective movement. Both integrity of the epithelium and ability to effectively heal the wound was found to depend on myosin mechanical cues. © 2014 Elsevier Inc. Source

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