Contributions of the LG modules and furin processing to laminin-2 functions

Sergei P. Smirnov, Erin L. McDearmon, Shaohua Li, James M. Ervasti, Karl Tryggvason, Peter D. Yurchenco

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

The α2-laminin subunit contributes to basement membrane functions in muscle, nerve, and other tissues, and mutations in its gene are causes of congenital muscular dystrophy. The α2 G-domain modules, mutated in several of these disorders, are thought to mediate different cellular interactions. To analyze these contributions, we expressed recombinant laminin-2 (α2β1γ1) with LG4-5, LG1-3, and LG1-5 modular deletions. Wild-type and LG4-5 deleted-laminins were isolated from medium intact and cleaved within LG3 by a furin-like convertase. Myoblasts adhered predominantly through LG1-3 while a-dystroglycan bound to both LG1-3 and LG4-5. Recombinant laminin stimulated acetylcholine receptor (AChR) clustering; however, clustering was induced only by the proteolytic processed form, even in the absence of LG4-5. Furthermore, clustering required α6β1 integrin and α-dystroglycan binding activities available on LG1-3, acting in concert with laminin polymerization. The ability of the modified laminins to mediate basement membrane assembly was also evaluated in embryoid bodies where it was found that both LG1-3 and LG4 -5, but not processing, were required. In conclusion, there is a division of labor among LG-modules in which (i) LG4-5 is required for basement membrane assembly but not for AChR clustering, and (ii) laminin-induced AChR clustering requires furin cleavage of LG3 as well as a-dystroglycan and α6β1 integrin binding.

Original languageEnglish (US)
Pages (from-to)18928-18937
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number21
DOIs
StatePublished - May 24 2002

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