scholarly journals BETA- AND GAMMA-SYNUCLEINS MODULATE SYNAPTIC VESICLE-BINDING OF ALPHA-SYNUCLEIN

2020 ◽  
Author(s):  
Kathryn E. Carnazza ◽  
Lauren Komer ◽  
André Pineda ◽  
Yoonmi Na ◽  
Trudy Ramlall ◽  
...  
Keyword(s):  
Nervous System ◽  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Direct Interaction ◽  
Alpha Synuclein ◽  
Snare Complex ◽  
Complex Assembly ◽  
Mutual Compensation ◽  
Conflicting Evidence

SUMMARYα-Synuclein (αSyn), β-synuclein (βSyn), and γ-synuclein (γSyn) are abundantly expressed in the vertebrate nervous system. αSyn functions in neurotransmitter release via binding to and clustering synaptic vesicles and chaperoning of SNARE-complex assembly. The functions of βSyn and γSyn are unknown. Functional redundancy of the three synucleins and mutual compensation when one synuclein is deleted have been proposed, but with conflicting evidence. Here, we demonstrate that βSyn and γSyn have a reduced affinity towards membranes compared to αSyn, and that direct interaction of βSyn or γSyn with αSyn results in reduced membrane binding of αSyn. Our data suggest that all three synucleins affect synapse function, but only αSyn mediates the downstream function of vesicle clustering and SNARE-complex assembly, while βSyn and γSyn modulate the activity of αSyn through regulating its binding to synaptic vesicles.

scholarly journals A new life for an old pump: V-ATPase and neurotransmitter release

2014 ◽  
Vol 205 (1) ◽  
pp. 7-9 ◽  
Author(s):  
Stefano Vavassori ◽  
Andreas Mayer
Keyword(s):  
Plasma Membrane ◽  
Complex Formation ◽  
Membrane Fusion ◽  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Snare Complex ◽  
Spontaneous Release ◽  
Synaptic Vesicle Fusion ◽  
Snare Complex Formation

Neurons fire by releasing neurotransmitters via fusion of synaptic vesicles with the plasma membrane. Fusion can be evoked by an incoming signal from a preceding neuron or can occur spontaneously. Synaptic vesicle fusion requires the formation of trans complexes between SNAREs as well as Ca2+ ions. Wang et al. (2014. J. Cell Biol. http://dx.doi.org/jcb.201312109) now find that the Ca2+-binding protein Calmodulin promotes spontaneous release and SNARE complex formation via its interaction with the V0 sector of the V-ATPase.

scholarly journals Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and αSNAP

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Eric A Prinslow ◽  
Karolina P Stepien ◽  
Yun-Zu Pan ◽  
Junjie Xu ◽  
Josep Rizo
Keyword(s):  
Complex Formation ◽  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Plasma Membranes ◽  
Snare Complex ◽  
Complex Assembly ◽  
Multiple Factors ◽  
Synaptotagmin 1 ◽  
Snare Complex Formation

Neurotransmitter release requires formation of trans-SNARE complexes between the synaptic vesicle and plasma membranes, which likely underlies synaptic vesicle priming to a release-ready state. It is unknown whether Munc18-1, Munc13-1, complexin-1 and synaptotagmin-1 are important for priming because they mediate trans-SNARE complex assembly and/or because they prevent trans-SNARE complex disassembly by NSF-αSNAP, which can lead to de-priming. Here we show that trans-SNARE complex formation in the presence of NSF-αSNAP requires both Munc18-1 and Munc13-1, as proposed previously, and is facilitated by synaptotagmin-1. Our data also show that Munc18-1, Munc13-1, complexin-1 and likely synaptotagmin-1 contribute to maintaining assembled trans-SNARE complexes in the presence of NSF-αSNAP. We propose a model whereby Munc18-1 and Munc13-1 are critical not only for mediating vesicle priming but also for precluding de-priming by preventing trans-SNARE complex disassembly; in this model, complexin-1 also impairs de-priming, while synaptotagmin-1 may assist in priming and hinder de-priming.

scholarly journals Microsecond Dissection of Neurotransmitter Release: SNARE-Complex Assembly Dictates Speed and Ca2+ Sensitivity

Neuron ◽  
2014 ◽  
Vol 82 (5) ◽  
pp. 1088-1100 ◽  
Author(s):  
Claudio Acuna ◽  
Qingchen Guo ◽  
Jacqueline Burré ◽  
Manu Sharma ◽  
Jianyuan Sun ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Snare Complex ◽  
Complex Assembly

Recent Breakthroughs in Neurotransmitter Release: Paradigm for Regulated Exocytosis?

Physiology ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 42-46
Author(s):  
G Thiel
Keyword(s):  
Synaptic Vesicle ◽  
Brain Function ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Vesicle Trafficking ◽  
Regulated Exocytosis ◽  
Intracellular Vesicle ◽  
Vesicle Cycle ◽  
Synaptic Vesicle Cycle

Synaptic vesicles play a fundamental role in brain function by mediating the release of neurotransmitters. Neurons do not use an entirely unique secretion apparatus but rather a modification of the general secretion machinery. Moreover, the synaptic vesicle cycle has many similarities with intracellular vesicle trafficking pathways.

Neurotransmitter Release

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Synaptic Cleft ◽  
Fusion Pore ◽  
Synaptic Membrane ◽  
Specialized Region ◽  
Synaptic Vesicle Fusion

The biochemical and physiological processes of neurotransmitter release from an active zone, a specialized region of synaptic membrane, are examined. Synaptic vesicles containing neurotransmitters are docked at the active zone and then primed for release by SNARE complexes that bring them into extreme proximity to the plasma membrane. Entry of calcium ions through voltage-gated calcium channels triggers synaptic vesicle fusion with the synaptic terminal membrane and the consequent diffusion of neurotransmitter into the synaptic cleft. Release results when the fusion pore bridging the synaptic vesicle and plasma membrane widens and neurotransmitter from the inside of the synaptic vesicle diffuses into the synaptic cleft. Membrane from the active zone membrane is endocytosed, and synaptic vesicle proteins are then reassembled into recycled synaptic vesicles, allowing for more rounds of neurotransmitter release.

scholarly journals Botulinum Neurotoxin a Blocks Synaptic Vesicle Exocytosis but Not Endocytosis at the Nerve Terminal

1999 ◽  
Vol 147 (6) ◽  
pp. 1249-1260 ◽  
Author(s):  
Elaine A. Neale ◽  
Linda M. Bowers ◽  
Min Jia ◽  
Karen E. Bateman ◽  
Lura C. Williamson
Keyword(s):  
Synaptic Vesicle ◽  
Nerve Terminal ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Botulinum Neurotoxin ◽  
Vesicle Membrane ◽  
Botulinum Neurotoxin A ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Botulinum Neurotoxins

The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis. Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis. We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis. In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K+-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins. In marked contrast, K+ depolarization, in the presence of Ca2+, triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A–blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles. These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca2+ is required for synaptic vesicle membrane retrieval.

scholarly journals μ2 adaptin facilitates but is not essential for synaptic vesicle recycling in Caenorhabditis elegans

2008 ◽  
Vol 183 (5) ◽  
pp. 881-892 ◽  
Author(s):  
Mingyu Gu ◽  
Kim Schuske ◽  
Shigeki Watanabe ◽  
Qiang Liu ◽  
Paul Baum ◽  
...  
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Evoked Responses ◽  
Nematode Caenorhabditis Elegans ◽  
Synaptic Vesicle Recycling ◽  
Specific Loss ◽  
Vesicle Recycling ◽  
Cargo Proteins

Synaptic vesicles must be recycled to sustain neurotransmission, in large part via clathrin-mediated endocytosis. Clathrin is recruited to endocytic sites on the plasma membrane by the AP2 adaptor complex. The medium subunit (μ2) of AP2 binds to cargo proteins and phosphatidylinositol-4,5-bisphosphate on the cell surface. Here, we characterize the apm-2 gene (also called dpy-23), which encodes the only μ2 subunit in the nematode Caenorhabditis elegans. APM-2 is highly expressed in the nervous system and is localized to synapses; yet specific loss of APM-2 in neurons does not affect locomotion. In apm-2 mutants, clathrin is mislocalized at synapses, and synaptic vesicle numbers and evoked responses are reduced to 60 and 65%, respectively. Collectively, these data suggest AP2 μ2 facilitates but is not essential for synaptic vesicle recycling.

scholarly journals Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

Neuron ◽  
2009 ◽  
Vol 62 (5) ◽  
pp. 683-694 ◽  
Author(s):  
Frédéric Darios ◽  
Catherine Wasser ◽  
Anastasia Shakirzyanova ◽  
Artur Giniatullin ◽  
Kerry Goodman ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Snare Complex ◽  
Complex Assembly ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

scholarly journals Conformational Change of Syntaxin-3b in Regulating SNARE Complex Assembly in the Ribbon Synapses

2021 ◽  
Author(s):  
Claire Gething ◽  
Joshua Ferrar ◽  
Bishal Misra ◽  
Giovanni Howells ◽  
Ucheor B. Choi
Keyword(s):  
Plasma Membrane ◽  
Complex Formation ◽  
Synaptic Vesicle ◽  
Conformational Change ◽  
Single Molecule ◽  
Conformational Changes ◽  
Snare Complex ◽  
Complex Assembly ◽  
Ribbon Synapses ◽  
Snare Complex Formation

AbstractNeurotransmitter release of synaptic vesicles relies on the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of syntaxin and SNAP-25 on the plasma membrane and synaptobrevin on the synaptic vesicle. The formation of the SNARE complex progressively zippers towards the membranes, which drives membrane fusion between the plasma membrane and the synaptic vesicle. However, the underlying molecular mechanism of SNARE complex regulation is unclear. In this study, we investigate the syntaxin-3b isoform found in the retinal ribbon synapses using single-molecule fluorescence resonance energy transfer (smFRET) to monitor the conformational changes of syntaxin-3b that modulate the SNARE complex formation. We found that syntaxin-3b is predominantly in a self-inhibiting closed conformation, inefficiently forming the ternary SNARE complex. Conversely, a phosphomimetic mutation (T14E) at the N-terminal region of syntaxin-3b promoted the open conformation, similar to the constitutively open form of syntaxin LE mutant. When syntaxin-3b is bound to Munc18-1, SNARE complex formation is almost completely blocked. Surprisingly, the T14E mutation of syntaxin-3b partially abolishes Munc18-1 regulation, acting as a conformational switch to trigger SNARE complex assembly. Thus, we suggest a model where the conformational change of syntaxin-3b induced by phosphorylation initiates the release of neurotransmitters in the ribbon synapses.

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