Distinct pools of synaptic vesicles in neurotransmitter release

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.

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Neurotransmitter Release

10.1093/med/9780190237493.003.0011 ◽

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.

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

The Journal of Cell Biology ◽

10.1083/jcb.147.6.1249 ◽

1999 ◽

Vol 147 (6) ◽

pp. 1249-1260 ◽

Cited By ~ 59

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.

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Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles

The Journal of Cell Biology ◽

10.1083/jcb.200710061 ◽

2007 ◽

Vol 179 (7) ◽

pp. 1481-1496 ◽

Cited By ~ 71

Author(s):

Tomoko Ohyama ◽

Patrik Verstreken ◽

Cindy V. Ly ◽

Tanja Rosenmund ◽

Akhila Rajan ◽

...

Keyword(s):

Neurotransmitter Release ◽

Synaptic Vesicles ◽

Protein Localization ◽

Low Frequency ◽

Chimeric Protein ◽

Interacting Protein ◽

Low Frequency Stimulation ◽

Frequency Stimulation ◽

And Function ◽

Huntingtin Interacting Protein

Posttranslational modification through palmitoylation regulates protein localization and function. In this study, we identify a role for the Drosophila melanogaster palmitoyl transferase Huntingtin-interacting protein 14 (HIP14) in neurotransmitter release. hip14 mutants show exocytic defects at low frequency stimulation and a nearly complete loss of synaptic transmission at higher temperature. Interestingly, two exocytic components known to be palmitoylated, cysteine string protein (CSP) and SNAP25, are severely mislocalized at hip14 mutant synapses. Complementary DNA rescue and localization experiments indicate that HIP14 is required solely in the nervous system and is essential for presynaptic function. Biochemical studies indicate that HIP14 palmitoylates CSP and that CSP is not palmitoylated in hip14 mutants. Furthermore, the hip14 exocytic defects can be suppressed by targeting CSP to synaptic vesicles using a chimeric protein approach. Our data indicate that HIP14 controls neurotransmitter release by regulating the trafficking of CSP to synapses.

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Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

The Journal of Cell Biology ◽

10.1083/jcb.201601098 ◽

2016 ◽

Vol 216 (1) ◽

pp. 231-246 ◽

Cited By ~ 29

Author(s):

Joseph J. Bruckner ◽

Hong Zhan ◽

Scott J. Gratz ◽

Monica Rao ◽

Fiona Ukken ◽

...

Keyword(s):

Neural Plasticity ◽

Active Zone ◽

Neurotransmitter Release ◽

Synaptic Vesicles ◽

Motor Behavior ◽

Molecular Organization ◽

Electrophysiological Studies ◽

Circuit Function ◽

Synaptic Vesicle Release ◽

Ca2 Channels

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.

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

The Journal of Cell Biology ◽

10.1083/jcb.201403040 ◽

2014 ◽

Vol 205 (1) ◽

pp. 7-9 ◽

Cited By ~ 11

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.

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Postsynaptic Neuroligin-1 Mediates Presynaptic Endocytosis During Neuronal Activity

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.744845 ◽

2021 ◽

Vol 14 ◽

Author(s):

Jiaqi Keith Luo ◽

Holly Melland ◽

Jess Nithianantharajah ◽

Sarah L. Gordon

Keyword(s):

Ampa Receptors ◽

Neurotransmitter Release ◽

Synaptic Vesicles ◽

High Fidelity ◽

Excitatory Synapses ◽

Synaptic Efficacy ◽

Molecular Architecture ◽

Adhesion Protein ◽

Presynaptic Nerve Terminal ◽

Presynaptic Release

Fast, high-fidelity neurotransmission and synaptic efficacy requires tightly regulated coordination of pre- and postsynaptic compartments and alignment of presynaptic release sites with postsynaptic receptor nanodomains. Neuroligin-1 (Nlgn1) is a postsynaptic cell-adhesion protein exclusively localised to excitatory synapses that is crucial for coordinating the transsynaptic alignment of presynaptic release sites with postsynaptic AMPA receptors as well as postsynaptic transmission and plasticity. However, little is understood about whether the postsynaptic machinery can mediate the molecular architecture and activity of the presynaptic nerve terminal, and thus it remains unclear whether there are presynaptic contributions to Nlgn1-dependent control of signalling and plasticity. Here, we employed a presynaptic reporter of neurotransmitter release and synaptic vesicle dynamics, synaptophysin-pHluorin (sypHy), to directly assess the presynaptic impact of loss of Nlgn1. We show that lack of Nlgn1 had no effect on the size of the readily releasable or entire recycling pool of synaptic vesicles, nor did it impact exocytosis. However, we observed significant changes in the retrieval of synaptic vesicles by compensatory endocytosis, specifically during activity. Our data extends growing evidence that synaptic adhesion molecules critical for forming transsynaptic scaffolds are also important for regulating activity-induced endocytosis at the presynapse.

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