Dynamic Ca2+-Dependent Stimulation of Vesicle Fusion by Membrane-Anchored Synaptotagmin 1
Abstract: Synaptotagmin1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca2+ levels rise. Although in vitro reconstitution experiments have failed to recapitulate Ca2+-triggered membrane fusion with the full-length, membrane-anchored Syt1, the genomic analysis indicates that all Syt isoforms except one preserve the transmembrane domain, suggesting a critical, but yet unknown, role of the membrane anchor in the Ca2+-induced neurotransmitter release. Using the in vitro single-vesicle fusion assay that tracks individual fusion events between a pair of 50-nm vesicles [1,2], we here report that the membrane-anchored Syt1 exhibits markedly enhanced Ca2+ sensitivity and fusion speed. With physiological 10 M Ca2+, Syt1 catalyzes the transition to full fusion within a few hundred msec. Unexpectedly, this stimulatory activity drops as the Ca2+ level rises, reaching complete inactivation of Syt1 at hundreds of M Ca2+, a non-monotonic behaviour different from a usual Michaelis-Menten enzyme. This stimulation pattern of Syt1 is the result of a ‘tug-of-war’ between cis- and trans-membrane interactions, which in turn critically depends on the molecular environments of fusing membranes. Therefore, Syt1 requires the membrane-anchor to stimulate Ca2+-induced vesicle fusion to physiological rates, as well as to function as a dynamic presynaptic Ca2+ switch that controls the probability of the neurotransmitter release [3].
* 일시 : 5월 27일 목요일 오후 4시 30분
* 장소 : 형남공학관 112호
* 연사 : 윤 태 영 교수 (KIAST 물리학과)