Cellular interaction of integrin alpha3beta1 with laminin 5 promotes gap junctional communication.
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 alpha3beta1, 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 alpha3beta1 with laminin 5 was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking alpha3beta1-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 alpha3beta1 promotes GJIC that integrates individual cells into synchronized epiboles.
Lampe
P D
PD
Divisions of Basic Sciences and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. plampe@fhcrc.org
Nguyen
B P
BP
Gil
S
S
Usui
M
M
Olerud
J
J
Takada
Y
Y
Carter
W G
WG
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D006224:Cricetinae; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000737:chemistry / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D017474:Receptors, Laminin / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012867:Skin / Q000166:cytology; D014162:Transfection; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D016023:Integrins; D017474:Receptors, Laminin; D011994:Recombinant Proteins; D000097794:Kalinin