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© The Rockefeller University Press, 0021-9525/1997//1583 $5.00
The Journal of Cell Biology, Volume 139, Number 6, , 1997 1583-1595

Article

Muscle β1D Integrin Reinforces the Cytoskeleton–Matrix Link: Modulation of Integrin Adhesive Function by Alternative Splicing



Alexey M. Belkin*, S. Francesco Retta{ddagger},{dagger}{dagger}, Olga Y. Pletjushkina§, Fiorella Balzac{ddagger}, Lorenzo Silengo{ddagger}, Reinhard Fassler||, Victor E. Koteliansky, Keith Burridge*, and Guido Tarone{ddagger},**

* Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, North Carolina 27599; {ddagger} Department of Biology, Genetics and Medical Chemistry, University of Torino, 10126 Torino, Italy; § Belozersky Institute of Physico-Chemical Biology, Moscow State University, 117311 Moscow, Russia; || Max-Planck-Institute for Biochemistry, Martinsried D-82152, Germany; Biogen Inc., Cambridge, Massachusetts 02142; ** Department of Psychology, University of Rome, Italy; and {dagger}{dagger} Institute of Biology, University of Palermo, 90133 Palermo, Italy

Expression of muscle-specific β1D integrin with an alternatively spliced cytoplasmic domain in CHO and GD25, β1 integrin-minus cells leads to their phenotypic conversion. β1D-transfected nonmuscle cells display rounded morphology, lack of pseudopodial activity, retarded spreading, reduced migration, and significantly enhanced contractility compared with their β1A-expressing counterparts. The transfected β1D is targeted to focal adhesions and efficiently displaces the endogenous β1A and {alpha}vβ3 integrins from the sites of cell–matrix contact. This displacement is observed on several types of extracellular matrix substrata and leads to elevated stability of focal adhesions in β1D transfectants. Whereas a significant part of cellular β1A integrin is extractable in digitonin, the majority of the transfected β1D is digitonin-insoluble and is strongly associated with the detergent-insoluble cytoskeleton. Increased interaction of β1D integrin with the actin cytoskeleton is consistent with and might be mediated by its enhanced binding to talin. In contrast, β1A interacts more strongly with {alpha}-actinin, than β1D. Inside-out driven activation of the β1D ectodomain increases ligand binding and fibronectin matrix assembly by β1D transfectants. Phenotypic effects of β1D integrin expression in nonmuscle cells are due to its enhanced interactions with both cytoskeletal and extracellular ligands. They parallel the transitions that muscle cells undergo during differentiation. Modulation of β1 integrin adhesive function by alternative splicing serves as a physiological mechanism reinforcing the cytoskeleton– matrix link in muscle cells. This reflects the major role for β1D integrin in muscle, where extremely stable association is required for contraction.

Address all correspondence to A.M. Belkin, Department of Biochemistry, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855. Tel.: (301) 738-0725. Fax: (301) 738-0794. E-mail: Belkina{at}usa.redcross.org


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