"Synapse formation and refinement at the neuromuscular junction"罗振革 博士（中科院神经生物研究所）-2010-10.22
报告题目：Synapse formation and refinement at the neuromuscular junction
报告人简介： 罗振革博士，中科院神经科学研究所研究员、教育和学位委员会主任，国家“杰出青年基金”获得者。近年来，在神经元极性建立、轴-树突发育和突触形成领域取得了系列研究成果。 获得“中国青年科技奖”和“上海市优秀学科带头人”等荣誉称号。研究方向主要是突触发育和可塑性研究，突触是神经传递的基本单元，其形成，发育及可塑性的研究是神经科学的核心问题之一。
报告简介：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.