Presynaptic Deletion of GIT Proteins Results in Increased Synaptic Strength at a Mammalian Central Synapse

Mónica S Montesinos; Wei Dong; Kevin Goff; Brati Das; Debbie Guerrero-Given; Robert Schmalzigaug; Richard T Premont; Rachel Satterfield; Naomi Kamasawa; Samuel M Young Jr

doi:10.1016/j.neuron.2015.10.042

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Presynaptic Deletion of GIT Proteins Results in Increased Synaptic Strength at a Mammalian Central Synapse

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Presynaptic Deletion of GIT Proteins Results in Increased Synaptic Strength at a Mammalian Central Synapse

Mónica S Montesinos, Wei Dong, Kevin Goff, Brati Das, Debbie Guerrero-Given, Robert Schmalzigaug, Richard T Premont, Rachel Satterfield, Naomi Kamasawa and Samuel M Young Jr

Neuron (Cambridge, Mass.), Vol.88(5), pp.918-925

12/02/2015

DOI: 10.1016/j.neuron.2015.10.042

PMCID: PMC4305191

PMID: 26637799

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Abstract

A cytomatrix of proteins at the presynaptic active zone (CAZ) controls the strength and speed of neurotransmitter release at synapses in response to action potentials. However, the functional role of many CAZ proteins and their respective isoforms remains unresolved. Here, we demonstrate that presynaptic deletion of the two G protein-coupled receptor kinase-interacting proteins (GITs), GIT1 and GIT2, at the mouse calyx of Held leads to a large increase in AP-evoked release with no change in the readily releasable pool size. Selective presynaptic GIT1 ablation identified a GIT1-specific role in regulating release probability that was largely responsible for increased synaptic strength. Increased synaptic strength was not due to changes in voltage-gated calcium channel currents or activation kinetics. Quantitative electron microscopy revealed unaltered ultrastructural parameters. Thus, our data uncover distinct roles for GIT1 and GIT2 in regulating neurotransmitter release strength, with GIT1 as a specific regulator of presynaptic release probability. •Presynaptic deletion of GITs increases AP-evoked release with no change in RRP size•Loss of GIT proteins does not affect voltage gated calcium currents•GIT1 has a specific role in regulating release probability, distinct from GIT2•GITs regulate synaptic strength by regulation of exocytosis efficiency Montesinos et al. report for the first time on GIT protein function in the mammalian presynaptic terminal. They demonstrate that GIT1 and GIT2 regulate synaptic strength by increasing exocytosis efficiency and identify GIT1 as a specific regulator of presynaptic release probability.

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Title: Subtitle: Presynaptic Deletion of GIT Proteins Results in Increased Synaptic Strength at a Mammalian Central Synapse
Creators: Mónica S Montesinos - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Wei Dong - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Kevin Goff - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Brati Das - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Debbie Guerrero-Given - Max Planck Florida Institute for Neuroscience Electron Microscopy Facility, Jupiter, FL 33458, USA
Robert Schmalzigaug - Divison of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Richard T Premont - Divison of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Rachel Satterfield - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Naomi Kamasawa - Max Planck Florida Institute for Neuroscience Electron Microscopy Facility, Jupiter, FL 33458, USA
Samuel M Young Jr - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.88(5), pp.918-925
Publisher: Elsevier Inc
DOI: 10.1016/j.neuron.2015.10.042
PMID: 26637799
PMCID: PMC4305191
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: DOI: 10.13039/501100004189, name: Max Planck Society; DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders, award: DC014093-01; DOI: 10.13039/100000002, name: NIH, award: R21 MH090556; DOI: 10.13039/100000005, name: DoD, award: W81XWH-11-2-0112
Language: English
Date published: 12/02/2015
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
Record Identifier: 9984025307702771

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