Conserved arginine residues in synaptotagmin 1 regulate fusion pore expansion through membrane contact
Year: 2021
Journal: Nat. Commun., Volume 12, FEB 3
Authors: Nyenhuis, Sarah B.; Karandikar, Nakul; Kiessling, Volker; Kreutzberger, Alex J. B.; Thapa, Anusa; Liang, Binyong; Tamm, Lukas K.; Cafiso, David S.
Organizations: NIH [NIGMS GM072694]
Synaptotagmin 1 is a vesicle-anchored membrane protein that functions as the Ca2+ sensor for synchronous neurotransmitter release. In this work, an arginine containing region in the second C2 domain of synaptotagmin 1 (C2B) is shown to control the expansion of the fusion pore and thereby the concentration of neurotransmitter released. This arginine apex, which is opposite the Ca2+ binding sites, interacts with membranes or membrane reconstituted SNAREs; however, only the membrane interactions occur under the conditions in which fusion takes place. Other regions of C2B influence the fusion probability and kinetics but do not control the expansion of the fusion pore. These data indicate that the C2B domain has at least two distinct molecular roles in the fusion event, and the data are consistent with a model where the arginine apex of C2B positions the domain at the curved membrane surface of the expanding fusion pore. Synaptotagmin 1 (Syt1) is the calcium sensor for fast synchronous neurotransmitter release but the mechanism by which it functions is still under debate. Here, the authors combine EPR measurements and functional studies and observe that different faces of the Syt1 C2B domain play different roles in regulating neurotransmitter release and they show that the expansion of the fusion pore is mediated by membrane contact of the C2B arginine apex.
