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CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse
In the presynaptic terminal, the magnitude and location of Ca(2+) entry through voltage-gated Ca(2+) 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 delete...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372087/ https://www.ncbi.nlm.nih.gov/pubmed/29996090 http://dx.doi.org/10.1016/j.celrep.2018.06.024 |
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author | Dong, Wei Radulovic, Tamara Goral, R. Oliver Thomas, Connon Montesinos, Monica Suarez Guerrero-Given, Debbie Hagiwara, Akari Putzke, Travis Hida, Yamato Abe, Manabu Sakimura, Kenji Kamasawa, Naomi Ohtsuka, Toshihisa Young, Samuel M. |
author_facet | Dong, Wei Radulovic, Tamara Goral, R. Oliver Thomas, Connon Montesinos, Monica Suarez Guerrero-Given, Debbie Hagiwara, Akari Putzke, Travis Hida, Yamato Abe, Manabu Sakimura, Kenji Kamasawa, Naomi Ohtsuka, Toshihisa Young, Samuel M. |
author_sort | Dong, Wei |
collection | PubMed |
description | In the presynaptic terminal, the magnitude and location of Ca(2+) entry through voltage-gated Ca(2+) 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(V)2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the Ca(V)2.1 current density with concomitant reductions in Ca(V)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(2+) channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of Ca(V)2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity. |
format | Online Article Text |
id | pubmed-6372087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-63720872019-02-12 CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse Dong, Wei Radulovic, Tamara Goral, R. Oliver Thomas, Connon Montesinos, Monica Suarez Guerrero-Given, Debbie Hagiwara, Akari Putzke, Travis Hida, Yamato Abe, Manabu Sakimura, Kenji Kamasawa, Naomi Ohtsuka, Toshihisa Young, Samuel M. Cell Rep Article In the presynaptic terminal, the magnitude and location of Ca(2+) entry through voltage-gated Ca(2+) 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(V)2.1 channel-exclusive presynaptic terminal. We found that loss of CAST/ELKS reduces the Ca(V)2.1 current density with concomitant reductions in Ca(V)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(2+) channel coupling is unchanged, but spontaneous release rates are elevated. Thus, our data identify distinct roles for CAST/ELKS as positive regulators of Ca(V)2.1 channel density and suggest that they regulate release probability through a post-priming step that controls synaptic vesicle fusogenicity. 2018-07-10 /pmc/articles/PMC6372087/ /pubmed/29996090 http://dx.doi.org/10.1016/j.celrep.2018.06.024 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dong, Wei Radulovic, Tamara Goral, R. Oliver Thomas, Connon Montesinos, Monica Suarez Guerrero-Given, Debbie Hagiwara, Akari Putzke, Travis Hida, Yamato Abe, Manabu Sakimura, Kenji Kamasawa, Naomi Ohtsuka, Toshihisa Young, Samuel M. CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse |
title | CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse |
title_full | CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse |
title_fullStr | CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse |
title_full_unstemmed | CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse |
title_short | CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse |
title_sort | cast/elks proteins control voltage-gated ca(2+) channel density and synaptic release probability at a mammalian central synapse |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372087/ https://www.ncbi.nlm.nih.gov/pubmed/29996090 http://dx.doi.org/10.1016/j.celrep.2018.06.024 |
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