scholarly journals Synaptotagmin-7 links fusion-activated Ca2+ entry and fusion pore dilation

2014 ◽  
Vol 127 (24) ◽  
pp. 5218-5227 ◽  
Author(s):  
K. Neuland ◽  
N. Sharma ◽  
M. Frick
Keyword(s):  
Fusion Pore ◽  
Pore Dilation

scholarly journals Synaptotagmin-Ca2+triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation

2006 ◽  
Vol 570 (2) ◽  
pp. 295-307 ◽  
Author(s):  
Chih-Tien Wang ◽  
Jihong Bai ◽  
Payne Y. Chang ◽  
Edwin R. Chapman ◽  
Meyer B. Jackson
Keyword(s):  
Pc12 Cells ◽  
Fusion Pore ◽  
Regulated Exocytosis ◽  
Pore Opening ◽  
Pore Dilation

scholarly journals Activity-Dependent Fusion Pore Dilation Mediated by a Dynamin I-Syndapin Pathway

2011 ◽  
Vol 100 (3) ◽  
pp. 408a
Author(s):  
Prattana Samasilp ◽  
Bryan Doreian ◽  
Shyue-An Chan ◽  
Corey Smith
Keyword(s):  
Fusion Pore ◽  
Pore Dilation ◽  
Dynamin I ◽  
Activity Dependent

scholarly journals Cdc42 controls the dilation of the exocytotic fusion pore by regulating membrane tension

2014 ◽  
Vol 25 (20) ◽  
pp. 3195-3209 ◽  
Author(s):  
Marine Bretou ◽  
Ouardane Jouannot ◽  
Isabelle Fanget ◽  
Paolo Pierobon ◽  
Nathanaël Larochette ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Neuroendocrine Cells ◽  
Fusion Pore ◽  
Membrane Tension ◽  
Release Process ◽  
Vesicle Exocytosis ◽  
Pore Dilation ◽  
Pore Enlargement

Membrane fusion underlies multiple processes, including exocytosis of hormones and neurotransmitters. Membrane fusion starts with the formation of a narrow fusion pore. Radial expansion of this pore completes the process and allows fast release of secretory compounds, but this step remains poorly understood. Here we show that inhibiting the expression of the small GTPase Cdc42 or preventing its activation with a dominant negative Cdc42 construct in human neuroendocrine cells impaired the release process by compromising fusion pore enlargement. Consequently the mode of vesicle exocytosis was shifted from full-collapse fusion to kiss-and-run. Remarkably, Cdc42-knockdown cells showed reduced membrane tension, and the artificial increase of membrane tension restored fusion pore enlargement. Moreover, inhibiting the motor protein myosin II by blebbistatin decreased membrane tension, as well as fusion pore dilation. We conclude that membrane tension is the driving force for fusion pore dilation and that Cdc42 is a key regulator of this force.

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

2019 ◽  
Author(s):  
Zhenyong Wu ◽  
Nadiv Dharan ◽  
Sathish Thiyagarajan ◽  
Ben O’Shaughnessy ◽  
Erdem Karatekin
Keyword(s):  
Membrane Fusion ◽  
Snare Complex ◽  
Snare Proteins ◽  
Fusion Pore ◽  
Calcium Sensor ◽  
Fusion Reactions ◽  
Synaptotagmin 1 ◽  
Pore Opening ◽  
Pore Dilation ◽  
Fusion Pores

ABSTRACTAll membrane fusion reactions proceed through an initial fusion pore, including calcium-triggered vesicular release of neurotransmitters and hormones. Expansion of this small pore to release cargo molecules 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, beyond its established role in coupling calcium influx to fusion pore opening. Our results suggest that fusion pore dilation by Syt1 requires interactions with SNAREs, PI(4,5)P2, and calcium. Pore opening was abolished by a mutation of the tandem C2 domain (C2AB) hydrophobic loops of Syt1, suggesting that their calcium-induced insertion into the membrane is required for pore opening. We propose that loop insertion is also required for pore expansion, but through a distinct mechanism. Mathematical modelling suggests that membrane insertion re-orients the C2 domains bound to the SNARE complex, rotating the SNARE complex so as to exert force on the membranes in a mechanical lever action that increases the intermembrane distance. The increased membrane separation provokes pore dilation to offset a bending energy penalty. We conclude that Syt1 assumes a critical role in calcium-dependent fusion pore dilation during neurotransmitter and hormone release.SIGNIFICANCE STATEMENTMembrane fusion is a fundamental biological process, required for development, infection by enveloped viruses, fertilization, intracellular trafficking, and calcium-triggered release of neurotransmitters and hormones when cargo-laden vesicles fuse with the plasma membrane. All membrane fusion reactions proceed through an initial, nanometer-sized fusion pore which can flicker open-closed multiple times before expanding or resealing. Pore expansion is required for efficient cargo release, but underlying mechanisms are poorly understood. Using a combination of single-pore measurements and quantitative modeling, we suggest that a complex between the neuronal calcium sensor Synaptotagmin-1 and the SNARE proteins together act as a calcium-sensitive mechanical lever to force the membranes apart and enlarge the pore.

scholarly journals Role of trans to cis Transition in Viral Fusion Pore Dilation

2017 ◽  
Vol 112 (3) ◽  
pp. 79a
Author(s):  
Brett E. Alcott ◽  
Zhenyong Wu ◽  
Josie Bircher ◽  
Erdem Karatekin ◽  
Ben O' Shaughnessy
Keyword(s):  
Fusion Pore ◽  
Viral Fusion ◽  
Pore Dilation

scholarly journals Fusion Pore Dilation by Synaptotagmin-1

2019 ◽  
Vol 116 (3) ◽  
pp. 526a
Author(s):  
Zhenyong Wu ◽  
Nadiv Dharan ◽  
Sathish Thiyagarajan ◽  
Ben O'Shaughnessy ◽  
Erdem Karatekin
Keyword(s):  
Fusion Pore ◽  
Synaptotagmin 1 ◽  
Pore Dilation

scholarly journals Membrane mechanics can account for fusion pore dilation in stages

1995 ◽  
Vol 69 (6) ◽  
pp. 2489-2500 ◽  
Author(s):  
Y.A. Chizmadzhev ◽  
F.S. Cohen ◽  
A. Shcherbakov ◽  
J. Zimmerberg
Keyword(s):  
Fusion Pore ◽  
Membrane Mechanics ◽  
Pore Dilation

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

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Zhenyong Wu ◽  
Nadiv Dharan ◽  
Zachary A McDargh ◽  
Sathish Thiyagarajan ◽  
Ben O'Shaughnessy ◽  
...  
Keyword(s):  
Snare Complex ◽  
Snare Proteins ◽  
Fusion Pore ◽  
C2 Domain ◽  
Calcium Sensor ◽  
Fusion Reactions ◽  
Small Pore ◽  
Synaptotagmin 1 ◽  
Pore Dilation ◽  
Fusion Pores

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.

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