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© The Rockefeller University Press, 0021-9525/1998//1735 $5.00
The Journal of Cell Biology, Volume 143, Number 6, , 1998 1735-1747

Cellular Interaction of Integrin 3β1 with Laminin 5 Promotes Gap Junctional Communication

Paul D. Lampe^*,, Beth P. Nguyen^*,, Susana Gil^*, Marcia Usui, John Olerud, Yoshikazu Takada^||, and William G. Carter^*,

^* Divisions of Basic Sciences and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; Department of Pathobiology and Division of Dermatology, University of Washington, Seattle, Washington 98105; and ^|| Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037

Wounding of skin activates epidermal cell migration over exposed dermal collagen and fibronectin and over laminin 5 secreted into the provisional basement membrane. Gap junctional intercellular communication (GJIC) has been proposed to integrate the individual motile cells into a synchronized colony. We found that outgrowths of human keratinocytes in wounds or epibole cultures display parallel changes in the expression of laminin 5, integrin 3β1, E-cadherin, and the gap junctional protein connexin 43. Adhesion of keratinocytes on laminin 5, collagen, and fibronectin was found to differentially regulate GJIC. When keratinocytes were adhered on laminin 5, both structural (assembly of connexin 43 in gap junctions) and functional (dye transfer) assays showed a two- to threefold increase compared with collagen and five- to eightfold over fibronectin. Based on studies with immobilized integrin antibody and integrin-transfected Chinese hamster ovary cells, the interaction of integrin 3β1 with laminin 5 was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking 3β1–laminin 5 interactions to GJIC indicated that protein trafficking and Rho signaling were both required. We suggest that adhesion of epithelial cells to laminin 5 in the basement membrane via 3β1 promotes GJIC that integrates individual cells into synchronized epiboles.

Key Words: gap junctions • integrins • laminin 5 • epidermis • intracellular protein trafficking

Abbreviations used in this paper: BFA, Brefeldin A; BM, basement membrane; Cx43, connexin 43; DN, dominant negative; ECM, extracellular matrix; GJIC, gap junctional intercellular communication; HD, hemidesmosome; HFK, human foreskin keratinocyte; KGM, keratinocyte growth medium; LPA, lysophosphatidic acid.

Address correspondence related to ECM–integrin interaction and signaling to William Carter, Fred Hutchinson Cancer Research Center, A3-015, 1100 Fairview Avenue North, Seattle, WA 98109. Tel.: (206) 667-4478. Fax: (206) 667-3331. E-mail: wcarter{at}fhcrc.org Address correspondence related to gap junctions to Paul Lampe, Fred Hutchinson Cancer Research Center, DE-320, 1100 Fairview Avenue North, Seattle, WA 98109. Tel.: (206) 667-4123. Fax: (206) 667-2537. E-mail: plampe{at}fhcrc.org

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