INTEGRINS MEDIATE ADHESION TO AGRIN AND MODULATE AGRIN SIGNALING

Agrin, a basal lamina-associated proteoglycan, is a crucial nerve-deri ved organizer of postsynaptic differentiation at the skeletal neuromus cular junction, Because integrins serve as cellular receptors for many basal lamina components, we asked whether agrin interacts with integr ins. Agrin-induced aggregation of acetylcholine receptors on cultured myotubes was completely blocked by antibodies to the beta 1 integrin s ubunit and partially blocked by antibodies to the alpha v integrin sub unit, Agrin-induced clustering mas also inhibited by antisense oligonu cleotides to alpha v and a peptide that blocks the alpha v binding sit e. Non-muscle cells that expressed alpha v and beta 1 integrin subunit s adhered to immobilized agrin, and this adhesion was blocked by anti- alpha v and anti-beta 1 antibodies. Integrin alpha v-negative cells th at did not adhere to agrin were rendered adherent by introduction of a lpha v, Together, these results implicate integrins, including alpha v beta 1, as components or modulators of agrin's signal transduction pa thway.