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© The Rockefeller University Press, 0021-9525/1999//619 $5.00
The Journal of Cell Biology, Volume 145, Number 3, , 1999 619-631


Regular Articles

Laminin Polymerization Induces a Receptor–Cytoskeleton Network



Holly Colognato, Donald A. Winkelmann, and Peter D. Yurchenco

Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

The transition of laminin from a monomeric to a polymerized state is thought to be a crucial step in the development of basement membranes and in the case of skeletal muscle, mutations in laminin can result in severe muscular dystrophies with basement membrane defects. We have evaluated laminin polymer and receptor interactions to determine the requirements for laminin assembly on a cell surface and investigated what cellular responses might be mediated by this transition. We found that on muscle cell surfaces, laminins preferentially polymerize while bound to receptors that included dystroglycan and {alpha}7β1 integrin. These receptor interactions are mediated through laminin COOH-terminal domains that are spatially and functionally distinct from NH2-terminal polymer binding sites. This receptor-facilitated self-assembly drives rearrangement of laminin into a cell-associated polygonal network, a process that also requires actin reorganization and tyrosine phosphorylation. As a result, dystroglycan and integrin redistribute into a reciprocal network as do cortical cytoskeleton components vinculin and dystrophin. Cytoskeletal and receptor reorganization is dependent on laminin polymerization and fails in response to receptor occupancy alone (nonpolymerizing laminin). Preferential polymerization of laminin on cell surfaces, and the resulting induction of cortical architecture, is a cooperative process requiring laminin– receptor ligation, receptor-facilitated self-assembly, actin reorganization, and signaling events.

Key Words: laminin • matrix assembly • muscular dystrophy • dystroglycan • integrin



Abbreviations used in this paper: AEBSF, p-aminoethylbenzenesulfonyl fluoride; CMD, congenital muscular dystrophy.

This project was supported by National Institutes of Health grants R01-DK36425 (to P.D. Yurchenco) and R01-AR38454 (to D.A. Winkelmann).



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