ABSTRACT
Agrin, a basal lamina-associated proteoglycan, is a crucial nerve-derived organizer of postsynaptic differentiation at the skeletal neuromuscular junction. Because integrins serve as cellular receptors for many basal lamina components, we asked whether agrin interacts with integrins. Agrin-induced aggregation of acetylcholine receptors on cultured myotubes was completely blocked by antibodies to the β1 integrin subunit and partially blocked by antibodies to the αv integrin subunit. Agrin-induced clustering was also inhibited by antisense oligonucleotides to αv and a peptide that blocks the αv binding site. Non-muscle cells that expressed αv and β1 integrin subunits adhered to immobilized agrin, and this adhesion was blocked by anti-αv and anti-β1 antibodies. Integrin αv-negative cells that did not adhere to agrin were rendered adherent by introduction of αv. Together, these results implicate integrins, including αvβ1, as components or modulators of agrin’s signal transduction pathway.
