Integrins mediate adhesion to agrin and modulate agrin signaling.
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 beta1 integrin subunit and partially blocked by antibodies to the alpha(v) integrin subunit. Agrin-induced clustering was also inhibited by antisense oligonucleotides to alpha(v) and a peptide that blocks the alpha(v) binding site. Non-muscle cells that expressed alpha(v) and beta1 integrin subunits adhered to immobilized agrin, and this adhesion was blocked by anti-alpha(v) and anti-beta1 antibodies. Integrin alpha(v)-negative cells that did not adhere to agrin were rendered adherent by introduction of alpha(v). Together, these results implicate integrins, including alpha(v)beta1, as components or modulators of agrin's signal transduction pathway.
Martin
P T
PT
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Sanes
J R
JR
D018171:Agrin / Q000502:physiology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology*; D002642:Chick Embryo; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D011485:Protein Binding; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000502:physiology*; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*
D018171:Agrin; D000906:Antibodies; D019012:Integrin beta1; D016023:Integrins; D011950:Receptors, Cholinergic; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C094340:integrin alphavbeta1