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Novel molecular mechanisms of release and catch of neural signals

開催日 2014/9/12
時間 17:10 - 19:10
会場 Room G(303)
Chairperson(s) 久保 義弘 / Yoshihiro Kubo (生理学研究所 神経機能素子研究部門 / Division of Biophysics and Neurobiology, National Institute of Physiological Science, Japan)
森 泰生 / Yasuo Mori (京都大学工学研究科・地球環境学 / Graduate of School Engineering and Environmental Studies, Kyoto University, Japan)

Transsynaptic channelosome: Non-conducting role of voltage gated calcium channels for presynaptic differentiation

  • S2-G-2-1
  • Hiroshi Nishimune:1 
  • 1:Dept. Anatomy and Cell Biology, Univ of Kansas, Sch of Medicine, Kansas City, USA 

Presynaptic voltage gated calcium channels are necessary to initiate synaptic transmission. Presynaptic active zones play essential roles for synaptic transmission as sites of synaptic vesicle accumulation and fusion with presynaptic membrane. Molecular mechanisms that organize active zones involve synapse organizer laminin &beta2, its specific receptor presynaptic voltage gated calcium channels, and active zone specific proteins including Bassoon. Laminin &beta2 binds to the extracellular domain of calcium channels and anchors them at presynaptic terminals. Anchored calcium channels function as a scaffolding protein and the cytosolic domains of the channels bind directly to active zone specific proteins. These protein interactions organize active zones at nerve terminals that are essential for effective neurotransmitter release. Furthermore, direct interactions of active zone proteins and calcium channels modify ion channel characteristics to support effective synaptic transmission.
Interestingly, large synapses maintain active zone densities during the postnatal development of the central and peripheral nervous system. However, loss of active zone occurs in aged neuromuscular junctions, and this active zone loss is likely to weaken synapses and cause denervation. Importantly, this active zone loss could be ameliorated by increasing the activity of pre- and postsynaptic cells in aged neuromuscular junctions.
Similar molecular mechanism seems to play a role in organizing active zones of the central nervous system. Lack of voltage gated calcium channel causes reductions of active zone number and active zone specific protein Bassoon at cerebellar synapses. An extracellular interaction of a ligand-calcium channel is necessary for the accumulation of active zone proteins in cultured cerebellar neurons and proper animal behavior. These results suggest that presynaptic active zones in the central and peripheral nervous system are organized by a general mechanism that utilizes presynaptic calcium channels as a receptor and a scaffolding protein.

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