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J. Biol. Chem., Vol. 279, Issue 39, 41047-41057, September 24, 2004
Regulation of Intercellular Adhesion Strength in Fibroblasts*![]() ![]() ![]() ¶![]() ![]() ![]()
From the
The regulation of adherens junction formation in cells of mesenchymal lineage is of critical importance in tumorigenesis but is poorly characterized. As actin filaments are crucial components of adherens junction assembly, we studied the role of gelsolin, a calcium-dependent, actin severing protein, in the formation of N-cadherin-mediated intercellular adhesions. With a homotypic, donor-acceptor cell model and plates or beads coated with recombinant N-cadherin-Fc chimeric protein, we found that gelsolin spatially co-localizes to, and is transiently associated with, cadherin adhesion complexes. Fibroblasts from gelsolin-null mice exhibited marked reductions in kinetics and strengthening of N-cadherin-dependent junctions when compared with wild-type cells. Experiments with lanthanum chloride (250 µM) showed that adhesion strength was dependent on entry of calcium ions subsequent to N-cadherin ligation. Cadherin-associated gelsolin severing activity was required for localized actin assembly as determined by rhodamine actin monomer incorporation onto actin barbed ends at intercellular adhesion sites. Scanning electron microscopy showed that gelsolin was an important determinant of actin filament architecture of adherens junctions at nascent N-cadherin-mediated contacts. These data indicate that increased actin barbed end generation by the severing activity of gelsolin associated with N-cadherin regulates intercellular adhesion strength.
Received for publication, June 14, 2004 * This project was supported by CIHR group, operating, major equipment, and maintenance grants (to C. A. G. M.), a CIHR postdoctoral fellowship (to T. Y. E. S.), and a CIHR NORTH Strategic Training studentship (to M. W. C. C.) The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed: Rm. 243, Fitzgerald Bldg., 150 College St., University of Toronto, Toronto, Ontario, Canada, M5S 3E2. Tel.: 416-978-6684; Fax: 416-978-5956; E-mail: t.elsayegh{at}utoronto.ca.
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