How synaptotagmin promotes membrane fusion.
Synaptic vesicles loaded with neurotransmitters are exocytosed in a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent manner after presynaptic depolarization induces calcium ion (Ca2+) influx. The Ca2+ sensor required for fast fusion is synaptotagmin-1. The activation energy of bilayer-bilayer fusion is very high (approximately 40 k(B)T). We found that, in response to Ca2+ binding, synaptotagmin-1 could promote SNARE-mediated fusion by lowering this activation barrier by inducing high positive curvature in target membranes on C2-domain membrane insertion. Thus, synaptotagmin-1 triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs. This mechanism may be widely used in membrane fusion.
Martens
Sascha
S
Medical Research Council-Laboratory of Molecular Biology, Hills Road, CB2 0QH Cambridge, UK.
Kozlov
Michael M
MM
McMahon
Harvey T
HT
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D008081:Liposomes; D008561:Membrane Fusion; D008954:Models, Biological; D051381:Rats; D050600:SNARE Proteins / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology* / Q000648:ultrastructure; D050863:Synaptotagmin I / Q000502:physiology*
D008081:Liposomes; D050600:SNARE Proteins; D050863:Synaptotagmin I; D002118:Calcium