Department of Chemistry, University of Virginia, Charlottesville, VA, USA.
Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.
Nat Commun. 2021 Feb 3;12(1):761. doi: 10.1038/s41467-021-21090-x.
Synaptotagmin 1 is a vesicle-anchored membrane protein that functions as the Ca 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 Ca 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.
突触融合蛋白 1 是一种囊泡锚定的膜蛋白，作为同步神经递质释放的 Ca 传感器发挥作用。在这项工作中，突触融合蛋白 1 的第二个 C2 结构域（C2B）中含精氨酸的区域被证明控制融合孔的扩展，从而控制神经递质的释放浓度。这个位于 Ca 结合位点对面的精氨酸顶点与膜或膜重建的 SNARE 相互作用；然而，只有在融合发生的条件下才会发生膜相互作用。C2B 的其他区域影响融合概率和动力学，但不控制融合孔的扩展。这些数据表明 C2B 结构域在融合事件中至少具有两个不同的分子作用，并且数据与 C2B 结构域的精氨酸顶点将该结构域定位在扩展的融合孔的弯曲膜表面的模型一致。
