title: Presynaptic Deletion of GIT Proteins Results in Increased Synaptic Strength at a Mammalian Central Synapse.
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.
authors.affiliation: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
authors.forename: Mónica S
authors.initials: MS
authors.lastname: Montesinos
authors.affiliation: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Goff
authors.affiliation: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA; Integrative Program in Biology and Neuroscience, Florida Atlantic University, Jupiter, FL 33458, USA.
authors.forename: Brati
authors.initials: B
authors.lastname: Das
authors.affiliation: Max Planck Florida Institute for Neuroscience Electron Microscopy Facility, Jupiter, FL 33458, USA.
authors.forename: Debbie
authors.initials: D
authors.lastname: Guerrero-Given
authors.affiliation: Divison of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schmalzigaug
authors.affiliation: Divison of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Premont
authors.affiliation: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Satterfield
authors.affiliation: Max Planck Florida Institute for Neuroscience Electron Microscopy Facility, Jupiter, FL 33458, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamasawa
authors.affiliation: Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA. Electronic address: sam.young@mpfi.org.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Young
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D001921:Brain / Q000166:cytology*; D018797:Cell Cycle Proteins / Q000172:deficiency* / Q000235:genetics; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000172:deficiency* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics; D011336:Probability; D013569:Synapses / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D014161:Transduction, Genetic; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; C120766:Git1 protein, mouse; C120767:Git2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D050599:Vesicular Glutamate Transport Protein 2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins