"Synapse formation and refinement at the neuromuscular junction"羅振革 博士（中科院神經生物研究所）-2010-10.22

時間：2010年10月22日 10:00

地點：腦功能重點實驗室一樓會議室

報告題目：Synapse formation and refinement at the neuromuscular junction

報告人：羅振革 博士

報告人簡介： 羅振革博士，中科院神經科學研究所研究員、教育和學位委員會主任，國家“杰出青年基金”獲得者。近年來，在神經元極性建立、軸-樹突發育和突觸形成領域取得了系列研究成果。 獲得“中國青年科技獎”和“上海市優秀學科帶頭人”等榮譽稱號。研究方向主要是突觸發育和可塑性研究，突觸是神經傳遞的基本單元，其形成，發育及可塑性的研究是神經科學的核心問題之一。

報告簡介：Neuromuscular synapses are formed between motor neurons and skeletal muscle fibers. AChRs are concentrated at the postsynaptic membrane, which guarantees efficient and accurate neurotransmission. AChR clustering is a dynamic process, whereby nascent clusters underneath nerve terminals are stabilized by agrin, a motor neuron derived glycoprotein, and the AChR-associated protein rapsyn. Meanwhile, motor neurons release negative signals to disperse non-innervated clusters and refine clusters at the synapses. Genetic studies suggest that ACh may serve as a negative signal. Such counteractive interaction leads to eventual dispersal of non-synaptic AChR rich-sites and formation of receptor clusters at the postjunctional membrane. However, the underlying mechanisms are not well understood. Calpains are a family of calcium-activated intracellular cysteine proteases, which are ubiquitously expressed in various mammalian cells. Recently, we found a role of calpain in regulating postsynaptic differentiation at the NMJ. The cholinergic stimulation increased calpain activity, and this in turn resulted in an accumulation of p25, a potent activator of Cdk5. Inhibition of calpain attenuated cholinergic agonist-induced dispersal of AChR clusters in cultured muscle cells and prevented the loss of AChR clusters in agrin mutant mice. We also investigated regulatory mechanisms of calpain activity and found that rapsyn interacted with calpain and inhibited the cleavage activity of calpain. Our recent results show that caspase-3, an effector caspase involved in apoptosis, is also involved in synapse refinement at the NMJ. Together these studies identify a critical signaling mechanism by which ACh destabilizes AChR clusters and reveal a novel function of rapsyn in regulating AChR clustering and NMJ formation.