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日本-中国神経科学学会合同シンポジウム:Neuronal signaling for development and plasticity
Joint Symposium of the Japan Neuroscience Society and the Chinese Society for Neuroscience:Neuronal signaling for development and plasticity

開催日 2014/9/12
時間 17:10 - 19:10
会場 Room C(502)
Chairperson(s) 上口 裕之 / Hiroyuki Kamiguchi (理研BSI神経成長機構 / RIKEN Brain Science Institute, Japan)

Non-apoptotic role of caspase-3 in synapse refinement

  • S2-C-3-1
  • Zhenge Luo:1 Jinyuan Wang:1 Fei Chen:1 Xiuqing Fu:1 Xiaohui Zhang:1 
  • 1:Institute of Neuroscience, Chinese Academy of Sciences, China 

The clustering of neurotransmitter receptors is a hallmark for postsynaptic differentiation. At the vertebrate neuromuscular junction (NMJ), the clustering of AChRs is believed to be regulated by positive and negative factors, which determine strengthening of innervated AChR clusters and dispersion of aneural clusters, respectively. The interplay between positive and negative signals results in the precise matching of motor nerve terminals to individual postsynaptic sites enriched with AChRs. However, the intracellular interplay between positive and negative signaling remains elusive.Here we demonstrate that caspase-3, the effector protease involved in apoptosis, mediates elimination of AChR clusters. We found that caspase-3 was activated by cholinergic stimulation of cultured muscle cells without inducing cell apoptosis and this activation was prevented by agrin. Interestingly, inhibition of caspase-3 attenuated ACh agonist- induced dispersion of AChR clusters. Furthermore, we identified Dishevelled1 (Dvl1), a Wnt signaling protein involved in AChR clustering, as the substrate of caspase-3. Blocking Dvl1 cleavage prevented induced dispersion of AChR clusters. Finally, inhibition or genetic ablation of caspase-3 or expression of caspae-3-resistant form of Dvl1 caused stabilization of aneural AChR clusters. Thus, caspase-3 plays an important role in the elimination of postsynaptic structures during the development of NMJs.

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