CAST/ELKS Proteins Control Voltage-Gated Ca 2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

Wei Dong; Tamara Radulovic; R Oliver Goral; Connon Thomas; Monica Suarez Montesinos; Debbie Guerrero-Given; Akari Hagiwara; Travis Putzke; Yamato Hida; Manabu Abe; Kenji Sakimura; Naomi Kamasawa; Toshihisa Ohtsuka; Samuel M Young Jr

doi:10.1016/j.celrep.2018.06.024

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CAST/ELKS Proteins Control Voltage-Gated Ca 2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

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CAST/ELKS Proteins Control Voltage-Gated Ca 2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse

Wei Dong, Tamara Radulovic, R Oliver Goral, Connon Thomas, Monica Suarez Montesinos, Debbie Guerrero-Given, Akari Hagiwara, Travis Putzke, Yamato Hida, Manabu Abe, …

Cell reports (Cambridge), Vol.24(2), pp.284-293.e6

07/10/2018

DOI: 10.1016/j.celrep.2018.06.024

PMCID: PMC6372087

PMID: 29996090

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Abstract

In the presynaptic terminal, the magnitude and location of Ca entry through voltage-gated Ca channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein family at the calyx of Held, a Ca 2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the Ca 2.1 current density with concomitant reductions in Ca 2.1 channel numbers and clusters. Surprisingly, deletion of CAST/ELKS increases release probability while decreasing the readily releasable pool, with no change in active zone ultrastructure. In addition, Ca channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of Ca 2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity.

Probability

Synaptic Transmission - physiology

Mice, Inbred C57BL

Nerve Tissue Proteins - deficiency

Neurotransmitter Agents - metabolism

Synapses - ultrastructure

Calcium Channels, N-Type - metabolism

Cytoskeletal Proteins - deficiency

Action Potentials - physiology

Nerve Tissue Proteins - metabolism

Animals

Carrier Proteins - metabolism

Synapses - metabolism

Cytoskeletal Proteins - metabolism

rab GTP-Binding Proteins

Kinetics

Ion Channel Gating

Details

Title: Subtitle: CAST/ELKS Proteins Control Voltage-Gated Ca 2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse
Creators: Wei Dong - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA; Key Laboratory of Medical Electrophysiology, Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
Tamara Radulovic - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA
R Oliver Goral - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA
Connon Thomas - Max Planck Florida Institute for Neuroscience Electron Microscopy Facility, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Monica Suarez Montesinos - 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, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Akari Hagiwara - Department of Biochemistry, University of Yamanashi, Yamanashi 409-3898, Japan
Travis Putzke - Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Yamato Hida - Department of Biochemistry, University of Yamanashi, Yamanashi 409-3898, Japan
Manabu Abe - Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Kenji Sakimura - Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
Naomi Kamasawa - Max Planck Florida Institute for Neuroscience Electron Microscopy Facility, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
Toshihisa Ohtsuka - Department of Biochemistry, University of Yamanashi, Yamanashi 409-3898, Japan. Electronic address: tohtsuka@yamanashi.ac.jp
Samuel M Young Jr - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA; Department of Otolaryngology, University of Iowa, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA; Aging Mind Brain Initiative, University of Iowa, Iowa City, IA 52242, USA. Electronic address: samuel-m-young@uiowa.edu
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.24(2), pp.284-293.e6
DOI: 10.1016/j.celrep.2018.06.024
PMID: 29996090
PMCID: PMC6372087
NLM abbreviation: Cell Rep
eISSN: 2211-1247
Publisher: United States
Grant note: R01 DC014093 / NIDCD NIH HHS
Language: English
Date published: 07/10/2018
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
Record Identifier: 9984025311202771

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