scholarly journals Author response: Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1

2020 ◽  
Author(s):  
Vincent Huson ◽  
Marieke Meijer ◽  
Rien Dekker ◽  
Mirelle ter Veer ◽  
Marvin Ruiter ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Energy Barrier ◽  
Vesicle Fusion ◽  
Author Response ◽  
Synaptotagmin 1 ◽  
Post Tetanic Potentiation ◽  
Synaptic Vesicle Fusion ◽  
Response Post

scholarly journals Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Vincent Huson ◽  
Marieke Meijer ◽  
Rien Dekker ◽  
Mirelle ter Veer ◽  
Marvin Ruiter ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Energy Barrier ◽  
Phorbol Esters ◽  
Release Kinetics ◽  
Vesicle Fusion ◽  
Tetanic Stimulation ◽  
Release Rates ◽  
Synaptotagmin 1 ◽  
Post Tetanic Potentiation ◽  
Synaptic Vesicle Fusion

Previously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1-independent mechanisms that lower the energy barrier and act additively with Syt1-dependent mechanisms to produce PTP by exerting multiplicative effects on release rates.

scholarly journals Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1

2020 ◽  
Author(s):  
Vincent Huson ◽  
Marieke Meijer ◽  
Rien Dekker ◽  
Mirelle ter Veer ◽  
Marvin Ruiter ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Energy Barrier ◽  
Phorbol Esters ◽  
Release Kinetics ◽  
Vesicle Fusion ◽  
Tetanic Stimulation ◽  
Release Rates ◽  
Synaptotagmin 1 ◽  
Post Tetanic Potentiation ◽  
Synaptic Vesicle Fusion

AbstractPreviously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1 dependent and independent mechanisms that lower the energy barrier independently in an additive manner to produce PTP by multiplication of release rates.

scholarly journals Author response: Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

2015 ◽  
Author(s):  
Sebastiaan Schotten ◽  
Marieke Meijer ◽  
Alexander Matthias Walter ◽  
Vincent Huson ◽  
Lauren Mamer ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Energy Barrier ◽  
Fusion Rate ◽  
Vesicle Fusion ◽  
Author Response ◽  
Additive Effects ◽  
Synaptic Vesicle Fusion

scholarly journals Synaptotagmin 1 clamps synaptic vesicle fusion in mammalian neurons independent of complexin

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nicholas A. Courtney ◽  
Huan Bao ◽  
Joseph S. Briguglio ◽  
Edwin R. Chapman
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Fusion ◽  
Snare Proteins ◽  
Major Focus ◽  
C2 Domains ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Synaptotagmin 1 ◽  
Synaptic Vesicle Fusion ◽  
C2a Domain

Abstract Synaptic vesicle (SV) exocytosis is mediated by SNARE proteins. Reconstituted SNAREs are constitutively active, so a major focus has been to identify fusion clamps that regulate their activity in synapses: the primary candidates are synaptotagmin (syt) 1 and complexin I/II. Syt1 is a Ca2+ sensor for SV release that binds Ca2+ via tandem C2-domains, C2A and C2B. Here, we first determined whether these C2-domains execute distinct functions. Remarkably, the C2B domain profoundly clamped all forms of SV fusion, despite synchronizing residual evoked release and rescuing the readily-releasable pool. Release was strongly enhanced by an adjacent C2A domain, and by the concurrent binding of complexin to trans-SNARE complexes. Knockdown of complexin had no impact on C2B-mediated clamping of fusion. We postulate that the C2B domain of syt1, independent of complexin, is the molecular clamp that arrests SVs prior to Ca2+-triggered fusion.

scholarly journals Munc13-1 C1 Domain Activation Lowers the Energy Barrier for Synaptic Vesicle Fusion

2007 ◽  
Vol 27 (5) ◽  
pp. 1200-1210 ◽  
Author(s):  
J. Basu ◽  
A. Betz ◽  
N. Brose ◽  
C. Rosenmund
Keyword(s):  
Synaptic Vesicle ◽  
Energy Barrier ◽  
Vesicle Fusion ◽  
C1 Domain ◽  
Synaptic Vesicle Fusion

scholarly journals Correction: Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Sebastiaan Schotten ◽  
Marieke Meijer ◽  
Alexander Matthias Walter ◽  
Vincent Huson ◽  
Lauren Mamer ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Energy Barrier ◽  
Fusion Rate ◽  
Vesicle Fusion ◽  
Additive Effects ◽  
Synaptic Vesicle Fusion

scholarly journals Author response: Complexin inhibits spontaneous release and synchronizes Ca2+-triggered synaptic vesicle fusion by distinct mechanisms

2014 ◽  
Author(s):  
Ying Lai ◽  
Jiajie Diao ◽  
Daniel J Cipriano ◽  
Yunxiang Zhang ◽  
Richard A Pfuetzner ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Fusion ◽  
Author Response ◽  
Spontaneous Release ◽  
Synaptic Vesicle Fusion
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