Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner

Synchronous 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 intact 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 active zones. 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.

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

10.1101/2020.01.30.926246 ◽

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.

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RIM proteins and their role in synapse function

Biological Chemistry ◽

10.1515/bc.2010.064 ◽

2010 ◽

Vol 391 (6) ◽

Cited By ~ 35

Author(s):

Tobias Mittelstaedt ◽

Elena Alvaréz-Baron ◽

Susanne Schoch

Keyword(s):

Synaptic Vesicle ◽

Active Zone ◽

Neurotransmitter Release ◽

Multidomain Proteins ◽

Short Term ◽

Presynaptic Nerve Terminal ◽

Presynaptic Plasticity ◽

Active Zones ◽

Synaptic Vesicle Release ◽

The Brain

Abstract Active zones are specialized areas of the plasma membrane in the presynaptic nerve terminal that mediate neurotransmitter release and synaptic plasticity. The multidomain proteins RIM1 and RIM2 are integral components of the cytomatrix at the active zone, interacting with most other active zone-enriched proteins as well as synaptic vesicle proteins. In the brain, RIMs are present in multiple isoforms (α, β, γ) diverging in their structural composition, which mediate overlapping and distinct functions. Here, we summarize recent findings about the specific roles of the various RIM isoforms in basic synaptic vesicle release as well as long- and short-term presynaptic plasticity.

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Decision letter: Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner

10.7554/elife.55443.sa1 ◽

2020 ◽

Keyword(s):

Synaptic Vesicle ◽

Dependent Manner ◽

Vesicle Release ◽

Synaptic Vesicle Release

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Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca2+ pump PMCA

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2106621118 ◽

2021 ◽

Vol 118 (28) ◽

pp. e2106621118

Author(s):

Niklas Krick ◽

Stefanie Ryglewski ◽

Aylin Pichler ◽

Arthur Bikbaev ◽

Torsten Götz ◽

...

Keyword(s):

Synaptic Vesicle ◽

Neurotransmitter Release ◽

Calcium Currents ◽

Short Term ◽

Triggered Release ◽

Presynaptic Terminals ◽

Dynamic Regulation ◽

Short Term Plasticity ◽

Separate Control ◽

Active Zones

Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca2+ signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)–triggered presynaptic Ca2+ entry remain unclear. Combining Drosophila genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Drosophila Cav2 homolog, Dmca1A or cacophony, and the Cav1 homolog, Dmca1D) but with spatial and functional separation. Cav2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Cav1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca2+ influx but has a small impact on release. Instead, L-type calcium currents through Cav1 fine-tune short-term plasticity and facilitate SV recycling. Separate control of SV exo- and endocytosis by AP-triggered presynaptic Ca2+ influx through different channels demands efficient measures to protect the neurotransmitter release machinery against Cav1-mediated Ca2+ influx. We show that the plasma membrane Ca2+ ATPase (PMCA) resides in between active zones and isolates Cav2-triggered release from Cav1-mediated dynamic regulation of recycling and short-term plasticity, two processes which Cav2 may also contribute to. As L-type Cav1 channels also localize next to PQ-type Cav2 channels within axon terminals of some central mammalian synapses, we propose that Cav2, Cav1, and PMCA act as a conserved functional triad that enables separate control of SV release and recycling rates in presynaptic terminals.

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Improved signaling as a result of randomness in synaptic vesicle release

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1513160112 ◽

2015 ◽

Vol 112 (48) ◽

pp. 14954-14959 ◽

Cited By ~ 11

Author(s):

Calvin Zhang ◽

Charles S. Peskin

Keyword(s):

Synaptic Vesicle ◽

Neurotransmitter Release ◽

Action Potentials ◽

Time Derivative ◽

Linear Filter ◽

Vesicle Release ◽

Optimal Linear ◽

The Central Nervous System ◽

Synaptic Vesicle Release ◽

Probabilistic Nature

The probabilistic nature of neurotransmitter release in synapses is believed to be one of the most significant sources of noise in the central nervous system. We show how p0, the probability of release per docked vesicle when an action potential arrives, affects the dynamics of the rate of vesicle release in response to changes in the rate of arrival of action potentials. Furthermore, we examine the theoretical capability of a synapse in the estimation of desired signals using information from the stochastic vesicle release events under the framework of optimal linear filter theory. We find that a small p0, such as 0.1, reduces the error in the reconstruction of the input, or in the reconstruction of the time derivative of the input, from the time series of vesicle release events. Our results imply that the probabilistic nature of synaptic vesicle release plays a direct functional role in synaptic transmission.

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