Actin 'purse string' filaments are anchored by E-cadherin-mediated adherens junctions at the leading edge of the epithelial wound, providing coordinated cell movement.
At the leading edge of healing embryonic epithelium, cables of actin filaments appear to extend from cell to cell, forming a ring around the wound circumference. It has been hypothesized that this actin filament cable functions as a contractile 'purse string' to facilitate wound closure. We have observed this cable in large, circular healing epithelial wounds in corneas of adult mice. To elucidate the role of the actin filament cable, we characterized the molecular components associated with the cell-cell junction where the actin filament cable inserts and with the actin filament cable itself, and we studied the effect of disruption of the cable using an E-cadherin function-blocking antibody, ECCD-1. Localization of E-cadherin and the direct association of catenins with actin filament cable at the cell-cell interface of the actin cable confirmed that the cell-cell junction associated with the actin filament cable is an adherens junction. The E-cadherin function-blocking antibody caused disruption of the actin filament cable and induction of prominent lamellipodial extensions on cells at the leading edge, leading to a ragged uneven epithelial wound margin. These data demonstrate that cell-to-cell associated E-cadherin molecules link the actin filament cable, forming a functional adherens junction, and that the actin filament cable plays a role in coordinating cell movement.
Danjo
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Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Gipson
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D000199:Actins / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D001667:Binding, Competitive / Q000276:immunology; D015820:Cadherins / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003315:Cornea / Q000166:cytology; D065306:Corneal Injuries; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology; D007365:Intercellular Junctions / Q000737:chemistry / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009218:Myosins / Q000378:metabolism; D011554:Pseudopodia / Q000737:chemistry / Q000502:physiology; D015534:Trans-Activators; D014945:Wound Healing / Q000502:physiology*; D051176:beta Catenin
D000199:Actins; D000906:Antibodies; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D015534:Trans-Activators; D051176:beta Catenin; D009218:Myosins