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.

中文翻译：

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神经元钙传感器Synaptotagmin-1和SNARE蛋白协同作用来扩大融合孔

所有膜融合反应均通过初始融合孔进行，包括钙触发的神经递质和激素的释放。扩大这个小孔以释放货物在能量上是昂贵的，并且受细胞调节，但是对机理的了解却很少。在这里，我们显示神经元/胞外钙传感器Synaptotagmin-1（Syt1）促进由SNARE蛋白诱导的融合孔的扩展。孔扩张依赖于钙诱导的Syt1串联C2域疏水环插入膜中，先前显示可重新定向C2域。数学模型表明，C2B重定向会旋转结合的SNARE复合物，从而以机械杠杆作用在膜上施加作用力，从而增加融合孔的高度，从而引起孔扩张以抵消弯曲能的损失。