ケージドペプチドを用いた、神経伝達物質放出におけるシナーフィンの機能解析

抄録

The release of neurotransmitters at synapses requires the temporally-ordered trafficking of synaptic vesicles. More than 20 proteins are involved in this process, including the SNARE proteins that participate in membrane fusion during exocytosis. To discern the specific role that each protein plays, it is necessary to sort out the temporal order in which they interact. Here we consider the timing of action of synaphin (also named as complexin), a SNARE-binding protein that plays an important role in calcium-triggered neurotransmitter release. A light-activated binding-site peptide was used to perturb the interaction of synaphin with SNARE proteins at precise time intervals before neurotransmitter release. We find that this peptide inhibits neurotransmitter release within 180 milliseconds before synaptic vesicles fuse with the presynaptic plasma membrane. These results indicate that synaphin binds to SNARE complex after synaptic vesicles dock but well before the fraction of a millisecond required for calcium ions to trigger synaptic vesicle fusion. These results are compatible with a role for synaphin in preparing trans-SNARE complexes for membrane fusion. [J Physiol Sci. 2006;56 Suppl:S19]