抄録
Clathrin-mediated endocytosis plays a key role in the recycling of synaptic vesicles in nerve terminals and amphiphysin I is one of the components of the molecular machinery involved in this process. Amphiphysin I mediates invagination and fission of synaptic vesicles in cooperation with dynamin. We found that amphiphysin I was cleaved to three fragments by treatment with high KCl (80 mM) and by high-frequency electrical stimulation in the mouse hippocampal slices. The cleavage sites were localized in the CLAP domain. The cleaved amphiphysin I was unable to interact with dynamin and disrupted the co-polymerization into a ring formation with dynamin and liposome in a cell-free system. The calpain-dependent cleavages inhibited clathrin-mediated endocytosis. Finally the amphiphysin I cleavages were found in the hippocampus of kainate-treated FVB/N mice and the cleavages inhibited the neural hyperexcitation of the mice. I will review these findings and discuss the role of calpain-dependent cleavages of amphiphysin I in protecting neurons against excitotoxicity and hyperexcitation. [J Physiol Sci. 2006;56 Suppl:S35]
