scholarly journals A continuum model of docking of synaptic vesicle to plasma membrane

2015 ◽  
Vol 12 (102) ◽  
pp. 20141119 ◽  
Author(s):  
Tianshu Liu ◽  
Pankaj Singh ◽  
James T. Jenkins ◽  
Anand Jagota ◽  
Maria Bykhovskaia ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Pore Formation ◽  
Continuum Model ◽  
Synaptic Cleft ◽  
Fusion Pore ◽  
Neuronal Membrane ◽  
Electrostatic Repulsion ◽  
Synaptic Vesicle Fusion

Neurotransmitter release from neuronal terminals is governed by synaptic vesicle fusion. Vesicles filled with transmitters are docked at the neuronal membrane by means of the SNARE machinery. After a series of events leading up to the fusion pore formation, neurotransmitters are released into the synaptic cleft. In this paper, we study the mechanics of the docking process. A continuum model is used to determine the deformation of a spherical vesicle and a plasma membrane, under the influence of SNARE-machinery forces and electrostatic repulsion. Our analysis provides information on the variation of in-plane stress in the membranes, which is known to affect fusion. Also, a simple model is proposed to study hemifusion.

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 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 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 Hydrodynamics govern the pre-fusion docking time of synaptic vesicles

2018 ◽  
Vol 15 (138) ◽  
pp. 20170818
Author(s):  
Pankaj Singh ◽  
Chung-Yuen Hui
Keyword(s):  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Driving Force ◽  
Lipid Membrane ◽  
Synaptic Cleft ◽  
Fusion Pore ◽  
Ribbon Synapses ◽  
Experimental Findings ◽  
Synaptic Vesicle Fusion ◽  
Ribbon Structures

Synaptic vesicle fusion is a crucial step in the neurotransmission process. Neurotransmitter-filled vesicles are pre-docked at the synapse by the mediation of ribbon structures and SNARE proteins at the ribbon synapses. An electrical impulse triggers the fusion process of pre-docked vesicles, leading to the formation of a fusion pore and subsequently resulting in the release of neurotransmitter into the synaptic cleft. In this study, a continuum model of lipid membrane along with lubrication theory is used to determine the traverse time of the synaptic vesicle under the influence of hydrodynamic forces. We find that the traverse time is strongly dependent on how fast the driving force decays or grows with closure of the gap between the vesicle and the plasma membrane. If the correct behaviour is chosen, the traverse time obtained is of the order of a few hundred milliseconds and lies within the experimentally obtained value of approximately 250 ms (Zenisek D, Steyer JA, Almers W. 2000 Nature 406 , 849–854 ( doi:10.1038/35022500 )). We hypothesize that there are two different force behaviours, which complies with the experimental findings of pre-fusion docking of synaptic vesicles at the ribbon synapses. The common theme in the proposed force models is that the driving force has to very rapidly increase or decrease with the amount of clamping.

scholarly journals Probing synaptic vesicle fusion by altering mechanical properties of the neuronal surface membrane

2008 ◽  
Vol 105 (46) ◽  
pp. 18018-18022 ◽  
Author(s):  
Yongling Zhu ◽  
Charles F. Stevens
Keyword(s):  
Mechanical Properties ◽  
Synaptic Vesicle ◽  
Surface Membrane ◽  
Fusion Pore ◽  
Neuronal Membrane ◽  
Mechanical Process ◽  
Synaptic Vesicle Exocytosis ◽  
Fusion Probability ◽  
Vesicle Exocytosis ◽  
Synaptic Vesicle Fusion

Because synaptic vesicle exocytosis is a nano-mechanical process, it should be influenced by the mechanical properties of the cell membrane to which the vesicle fuses. By dissolving surfactants at various concentrations in the neuronal membrane, we have perturbed mechanical properties of the membrane and have found that dissolved surfactants lower the probability that a synaptic vesicle will open its fusion pore when the fusion machinery of the vesicle is activated by binding calcium. By using standard theories from the physics and chemistry of surfaces, we can account for this decrease in fusion probability and can infer that a vesicle, when activated, opens its fusion pore ≈3 times out of 4 and that the area of the fusion pore is ≈4 nm2.

scholarly journals Molecular Mechanisms of Fast Neurotransmitter Release

2018 ◽  
Vol 47 (1) ◽  
pp. 469-497 ◽  
Author(s):  
Axel T. Brunger ◽  
Ucheor B. Choi ◽  
Ying Lai ◽  
Jeremy Leitz ◽  
Qiangjun Zhou
Keyword(s):  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
High Speed ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Vesicle Fusion ◽  
Synaptic Proteins ◽  
Functional Studies ◽  
Protein Receptors ◽  
Synaptic Vesicle Fusion

This review summarizes current knowledge of synaptic proteins that are central to synaptic vesicle fusion in presynaptic active zones, including SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for neurotransmitter release. Structural and functional studies of the synaptic fusion machinery suggest new molecular models of synaptic vesicle priming and Ca2+-triggered fusion. These studies will be a stepping-stone toward answering the question of how the synaptic vesicle fusion machinery achieves such high speed and sensitivity.

scholarly journals Fusion Pore Diameter Regulation by Cations Modulating Local Membrane Anisotropy

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Doron Kabaso ◽  
Ana I. Calejo ◽  
Jernej Jorgačevski ◽  
Marko Kreft ◽  
Robert Zorec ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Continuum Model ◽  
Pore Diameter ◽  
Fusion Pore ◽  
Spontaneous Curvature ◽  
Local Concentration ◽  
Vesicle Membrane ◽  
Membrane Elasticity ◽  
Opening And Closing ◽  
Pore Dynamics

The fusion pore is an aqueous channel that is formed upon the fusion of the vesicle membrane with the plasma membrane. Once the pore is open, it may close again (transient fusion) or widen completely (full fusion) to permit vesicle cargo discharge. While repetitive transient fusion pore openings of the vesicle with the plasma membrane have been observed in the absence of stimulation, their frequency can be further increased using a cAMP-increasing agent that drives the opening of nonspecific cation channels. Our model hypothesis is that the openings and closings of the fusion pore are driven by changes in the local concentration of cations in the connected vesicle. The proposed mechanism of fusion pore dynamics is considered as follows: when the fusion pore is closed or is extremely narrow, the accumulation of cations in the vesicle (increased cation concentration) likely leads to lipid demixing at the fusion pore. This process may affect local membrane anisotropy, which reduces the spontaneous curvature and thus leads to the opening of the fusion pore. Based on the theory of membrane elasticity, we used a continuum model to explain the rhythmic opening and closing of the fusion pore.

scholarly journals Nanobodies reveal an extra-synaptic population of SNAP-25 and Syntaxin 1A in hippocampal neurons

2018 ◽  
Author(s):  
Manuel Maidorn ◽  
Aurélien Olichon ◽  
Silvio O. Rizzoli ◽  
Felipe Opazo
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Hippocampal Neurons ◽  
Cellular Localization ◽  
Super Resolution ◽  
Syntaxin 1A ◽  
Resolution Imaging ◽  
Single Domain Antibodies ◽  
The Subject ◽  
Synaptic Vesicle Fusion

AbstractSynaptic vesicle fusion (exocytosis) is a precisely regulated process that entails the formation of SNARE complexes between the vesicle protein synaptobrevin 2 (VAMP2) and the plasma membrane proteins Syntaxin 1 and SNAP-25. The sub-cellular localization of the latter two molecules remains unclear, although they have been the subject of many recent investigations. To address this, we generated two novel camelid single domain antibodies (nanobodies) specifically binding to SNAP-25 and Syntaxin 1A. These probes penetrated more easily into samples and detected their targets more efficiently than conventional antibodies in crowded regions. When investigated by super-resolution imaging, the nanobodies revealed substantial extra-synaptic populations for both SNAP-25 and Syntaxin 1A, which were poorly detected by antibodies. Moreover, extra-synaptic Syntaxin 1A molecules were recruited to synapses during stimulation, suggesting that these are physiologically-active molecules. We conclude that nanobodies are able to reveal qualitatively and quantitatively different organization patterns, when compared to conventional antibodies.

scholarly journals A novel region in the CaV2.1 α1 subunit C-terminus regulates fast synaptic vesicle fusion and vesicle docking at the mammalian presynaptic active zone

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Matthias Lübbert ◽  
R Oliver Goral ◽  
Rachel Satterfield ◽  
Travis Putzke ◽  
Arn MJM van den Maagdenberg ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Physical Distance ◽  
Subunit C ◽  
Vesicle Docking ◽  
C Terminus ◽  
Synaptic Vesicle Release ◽  
Synaptic Vesicle Fusion ◽  
Α1 Subunit

In central nervous system (CNS) synapses, action potential-evoked neurotransmitter release is principally mediated by CaV2.1 calcium channels (CaV2.1) and is highly dependent on the physical distance between CaV2.1 and synaptic vesicles (coupling). Although various active zone proteins are proposed to control coupling and abundance of CaV2.1 through direct interactions with the CaV2.1 α1 subunit C-terminus at the active zone, the role of these interaction partners is controversial. To define the intrinsic motifs that regulate coupling, we expressed mutant CaV2.1 α1 subunits on a CaV2.1 null background at the calyx of Held presynaptic terminal. Our results identified a region that directly controlled fast synaptic vesicle release and vesicle docking at the active zone independent of CaV2.1 abundance. In addition, proposed individual direct interactions with active zone proteins are insufficient for CaV2.1 abundance and coupling. Therefore, our work advances our molecular understanding of CaV2.1 regulation of neurotransmitter release in mammalian CNS synapses.

scholarly journals Transmembrane tethering of synaptotagmin to synaptic vesicles controls multiple modes of neurotransmitter release

2015 ◽  
Vol 112 (12) ◽  
pp. 3793-3798 ◽  
Author(s):  
Jihye Lee ◽  
J. Troy Littleton
Keyword(s):  
Plasma Membrane ◽  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Temporal Dynamics ◽  
Transgenic Animals ◽  
Vesicle Fusion ◽  
Full Length ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
C2 Domains

Synaptotagmin 1 (Syt1) is a synaptic vesicle integral membrane protein that regulates neurotransmitter release by activating fast synchronous fusion and suppressing slower asynchronous release. The cytoplasmic C2 domains of Syt1 interact with SNAREs and plasma membrane phospholipids in a Ca2+-dependent manner and can substitute for full-length Syt1 in in vitro membrane fusion assays. To determine whether synaptic vesicle tethering of Syt1 is required for normal fusion in vivo, we performed a structure-function study with tethering mutants at the Drosophila larval neuromuscular junction. Transgenic animals expressing only the cytoplasmic C2 domains or full-length Syt1 tethered to the plasma membrane failed to restore synchronous synaptic vesicle fusion, and also failed to clamp spontaneous vesicle release. In addition, transgenic animals with shorter, but not those with longer, linker regions separating the C2 domains from the transmembrane segment abolished Syt1’s ability to activate synchronous vesicle fusion. Similar defects were observed when C2 domain alignment was altered to C2B-C2A from the normal C2A-C2B orientation, leaving the tether itself intact. Although cytoplasmic and plasma membrane-tethered Syt1 variants could not restore synchronous release in syt1 null mutants, they were very effective in promoting fusion through the slower asynchronous pathway. As such, the subcellular localization of Syt1 within synaptic terminals is important for the temporal dynamics that underlie synchronous and asynchronous neurotransmitter release.

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