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 de...

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Published in:eLife
Main Authors: Zhuo Guan, Monica C Quiñones-Frías, Yulia Akbergenova, J Troy Littleton
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-04-01
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Online Access:https://elifesciences.org/articles/55443
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author Zhuo Guan
Monica C Quiñones-Frías
Yulia Akbergenova
J Troy Littleton
author_facet Zhuo Guan
Monica C Quiñones-Frías
Yulia Akbergenova
J Troy Littleton
author_sort Zhuo Guan
collection DOAJ
container_title eLife
description 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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spelling doaj-art-e4534965bc0e4d46978afeb75b413c4d2025-08-19T21:18:29ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.55443Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent mannerZhuo Guan0Monica C Quiñones-Frías1Yulia Akbergenova2J Troy Littleton3https://orcid.org/0000-0001-5576-2887The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United StatesThe Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United StatesThe Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United StatesThe Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United StatesSynchronous 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.https://elifesciences.org/articles/55443Synaptotagminneurotransmitter releaseexocytosissynapseready-releasable poolsynaptic vesicle
spellingShingle Zhuo Guan
Monica C Quiñones-Frías
Yulia Akbergenova
J Troy Littleton
Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner
Synaptotagmin
neurotransmitter release
exocytosis
synapse
ready-releasable pool
synaptic vesicle
title Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner
title_full Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner
title_fullStr Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner
title_full_unstemmed Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner
title_short Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner
title_sort drosophila synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage dependent manner
topic Synaptotagmin
neurotransmitter release
exocytosis
synapse
ready-releasable pool
synaptic vesicle
url https://elifesciences.org/articles/55443
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