scholarly journals Identification of a human synaptotagmin-1 mutation that perturbs synaptic vesicle cycling

2015 ◽  
Author(s):  
Kate Baker ◽  
Sarah L. Gordon ◽  
Detelina Grozeva ◽  
Margriet van Kogelenberg ◽  
Nicola Y. Roberts ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Cycling ◽  
Synaptotagmin 1

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 A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis

Cell ◽  
2006 ◽  
Vol 126 (6) ◽  
pp. 1175-1187 ◽  
Author(s):  
Jiong Tang ◽  
Anton Maximov ◽  
Ok-Ho Shin ◽  
Han Dai ◽  
Josep Rizo ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Synaptotagmin 1

Synaptic vesicle cycling at type-identified diaphragm neuromuscular junctions

2004 ◽  
Vol 30 (6) ◽  
pp. 774-783 ◽  
Author(s):  
Carlos B. Mantilla ◽  
Katharine L. Rowley ◽  
Mohamed A. Fahim ◽  
Wen-Zhi Zhan ◽  
Gary C. Sieck
Keyword(s):  
Synaptic Vesicle ◽  
Neuromuscular Junctions ◽  
Vesicle Cycling

scholarly journals Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle fusion and replenishment in a dosage-dependent manner

2020 ◽  
Author(s):  
Zhuo Guan ◽  
Mónica C. Quiñones-Frías ◽  
Yulia Akbergenova ◽  
J. Troy Littleton
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Dependent Manner ◽  
Short Term ◽  
Sensor Model ◽  
Synaptotagmin 1 ◽  
Asynchronous Release ◽  
Synaptic Vesicle Fusion

AbstractSynchronous neurotransmitter release is triggered by Ca2+ binding to the synaptic vesicle protein Synaptotagmin 1, while asynchronous fusion and short-term facilitation is hypothesized to be mediated by plasma membrane-localized Synaptotagmin 7 (SYT7). We generated mutations in Drosophila Syt7 to determine if it plays a conserved role as the Ca2+ sensor for these processes. Electrophysiology and quantal imaging revealed evoked release was elevated 2-fold. Syt7 mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and robust facilitation. Syt1/Syt7 double mutants displayed more release than Syt1 mutants alone, indicating SYT7 does not mediate the residual asynchronous release remaining in the absence of SYT1. SYT7 localizes to an internal membrane tubular network within the peri-active zone, but does not enrich at release sites. These findings indicate the two Ca2+ sensor model of SYT1 and SYT7 mediating all phases of neurotransmitter release and facilitation is not applicable at Drosophila synapses.

scholarly journals Ring-like oligomers of Synaptotagmins and related C2 domain proteins

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Maria N Zanetti ◽  
Oscar D Bello ◽  
Jing Wang ◽  
Jeff Coleman ◽  
Yiying Cai ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Synaptic Transmission ◽  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Structural Aspect ◽  
C2 Domain ◽  
Early Step ◽  
Vesicle Docking ◽  
Ring Assembly ◽  
Synaptotagmin 1

We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca2+ involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca2+ influx.

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