Ca2+-free synaptotagmin-1 binds to neuronal SNARE complexes anchored on nanodiscs, and Ca2+ releases this interaction to induce tight, specific binding to PIP2-containing membranes.
Janus RL Kobbersmed, Manon MM Berns ... Alexander M Walter
A mathematical model of neurotransmitter release predicts that a mutual stabilization of calcium and membrane phospholipids binding to synaptotagmin proteins allows several synaptotagmins to work together for fast synaptic transmission.
Bassam Tawfik, Joana S Martins ... Jakob Balslev Sørensen
Synaptotagmin-7 acts synergistically with synaptotagmin-1 by placing vesicles close to the plasma membrane within reach of the SNARE/Munc13-complex, supporting their priming and setting the stage for fast and slow fusion.
Novel insights into the molecular mechanisms underlying neurotransmitter release are provided by all-atom molecular dynamics simulations including SNARE proteins, synaptotagmin-1, complexin-1, a vesicle and a flat bilayer.
Experiments in C. elegans reveal how synaptotagmin and Rab3, the 'yin and yang' of synapses, control whether transmitter vesicles remain docked at the presynaptic membrane or release their contents into the synapse.
Two acidic membrane lipids increase synaptotagmin-1 dwell time and penetration into the membrane, reducing the membrane dissociation of synaptotagmin-1.
Sathish Ramakrishnan, Manindra Bera ... Shyam S Krishnakumar
Cooperative action of synaptotagmin and complexin is needed to arrest all SNARE complexes on a vesicle, and the reversal of the synaptotagmin clamp is sufficient to achieve fast, Ca2+-synchronized fusion.
Maria N Zanetti, Oscar D Bello ... Shyam S Krishnakumar
A model for synchronous neurotransmitter release suggests that when not in the presence of calcium ions, Synaptotagmin proteins form ring-like structures between the vesicle and plasma membrane that prevent spontaneous fusion.
During neurotransmitter release, calcium-induced membrane insertion of the C2B domain of Synaptotagmin re-orients the bound SNARE complex which dilates the fusion pore in a mechanical lever action.