The neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores

eLife

Zhenyong Wu¹  Erdem Karatekin²  Zachary A McDargh³  Sathish Thiyagarajan³  Nadiv Dharan³  Ben O'Shaughnessy³ 

[1] Department of Cellular and Molecular Physiology, Yale University, New Haven, United States;Nanobiology Institute, Yale University, West Haven, United States;Department of Cellular and Molecular Physiology, Yale University, New Haven, United States;Nanobiology Institute, Yale University, West Haven, United States;Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States;Saints-Pères Paris Institute for the Neurosciences (SPPIN), Université de Paris, Centre National de la Recherche Scientifique (CNRS) UMR 8003, Paris, France;Department of Chemical Engineering, Columbia University, New York, United States;

关键词: exocytosis;    SNARE proteins;    Synaptotagmin-1;    calcium-triggered neurotransmitter release;    membrane fusion;    fusion pore;    None;   

DOI  :  10.7554/eLife.68215

来源: eLife Sciences Publications, Ltd

【 摘 要 】

All membrane fusion reactions proceed through an initial fusion pore, including calcium-triggered release of neurotransmitters and hormones. Expansion of this small pore to release cargo is energetically costly and regulated by cells, but the mechanisms are poorly understood. Here, we show that the neuronal/exocytic calcium sensor Synaptotagmin-1 (Syt1) promotes expansion of fusion pores induced by SNARE proteins. Pore dilation relied on calcium-induced insertion of the tandem C2 domain hydrophobic loops of Syt1 into the membrane, previously shown to reorient the C2 domain. Mathematical modelling suggests that C2B reorientation rotates a bound SNARE complex so that it exerts force on the membranes in a mechanical lever action that increases the height of the fusion pore, provoking pore dilation to offset the bending energy penalty. We conclude that Syt1 exerts novel non-local calcium-dependent mechanical forces on fusion pores that dilate pores and assist neurotransmitter and hormone release.

【 授权许可】

CC BY