Nitric oxide and cyclic GMP regulate early events in agrin signaling in skeletal muscle cells.

摘要: Abstract Agrin released from motor nerve terminals directs differentiation of the vertebrate neuromuscular junction (NMJ). Activity nitric oxide synthase (NOS), guanylate cyclase (GC), and cyclic GMP-dependent protein kinase (PKG) contributes to agrin signaling in embryonic frog chick muscle cells. Stimulation NO/cyclic GMP (cGMP) pathway embryos potentiates agrin's ability aggregate acetylcholine receptors (AChRs) at NMJs. Here we investigated timing mechanism NO cGMP action. increased levels mouse C2C12 myotubes. donors potentiated agrin-induced AChR aggregation during first 20 min treatment, but overnight treatment with inhibited activity. Adenoviruses encoding siRNAs against each three NOS isoforms reduced activity, indicating that these all contribute signaling. Inhibitors NOS, GC, or PKG cells by ∼ 50%. However, activation GTPase Rac1, an early step signaling, was dependent on activity mimicked a analog. Our results indicate stimulation NO/cGMP is important few minutes required for Rac1 activation, key leading reorganization actin cytoskeleton subsequent AChRs surface skeletal