Martin P T, Sanes J R
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Development. 1997 Oct;124(19):3909-17. doi: 10.1242/dev.124.19.3909.
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.
聚集蛋白是一种与基底层相关的蛋白聚糖，是骨骼肌神经肌肉接头处突触后分化的关键神经源性组织者。由于整合素作为许多基底层成分的细胞受体，我们探究了聚集蛋白是否与整合素相互作用。抗β1整合素亚基的抗体完全阻断了聚集蛋白诱导培养肌管上乙酰胆碱受体的聚集，抗α(v)整合素亚基的抗体部分阻断了该聚集。抗α(v)的反义寡核苷酸和阻断α(v)结合位点的肽也抑制了聚集蛋白诱导的聚集。表达α(v)和β1整合素亚基的非肌肉细胞黏附于固定化的聚集蛋白，这种黏附被抗α(v)和抗β1抗体阻断。不黏附于聚集蛋白的整合素α(v)阴性细胞通过导入α(v)而变得具有黏附性。这些结果共同表明，包括α(v)β1在内的整合素是聚集蛋白信号转导途径的组成部分或调节剂。
