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PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons
PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that PERK regulates Ca(2+) dynamics in insulin-secreting β-cells underlying glucose-...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045583/ https://www.ncbi.nlm.nih.gov/pubmed/27716400 http://dx.doi.org/10.1186/s13041-016-0268-5 |
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author | Zhu, Siying McGrath, Barbara C. Bai, Yuting Tang, Xin Cavener, Douglas R. |
author_facet | Zhu, Siying McGrath, Barbara C. Bai, Yuting Tang, Xin Cavener, Douglas R. |
author_sort | Zhu, Siying |
collection | PubMed |
description | PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that PERK regulates Ca(2+) dynamics in insulin-secreting β-cells underlying glucose-stimulated insulin secretion, and modulates Ca(2+) signals-dependent working memory, we explored the role of PERK in regulating G(q) protein-coupled Ca(2+) dynamics in pyramidal neurons. We found that acute PERK inhibition by the use of a highly specific PERK inhibitor reduced the intracellular Ca(2+) rise stimulated by the activation of acetylcholine, metabotropic glutamate and bradykinin-2 receptors in primary cortical neurons. More specifically, acute PERK inhibition increased IP(3) receptor mediated ER Ca(2+) release, but decreased receptor-operated extracellular Ca(2+) influx. Impaired G(q) protein-coupled intracellular Ca(2+) rise was also observed in genetic Perk knockout neurons. Taken together, our findings reveal a novel role of PERK in neurons, which is eIF2α-independent, and suggest that the impaired working memory in forebrain-specific Perk knockout mice may stem from altered G(q) protein-coupled intracellular Ca(2+) dynamics in cortical pyramidal neurons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-016-0268-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5045583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50455832016-10-12 PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons Zhu, Siying McGrath, Barbara C. Bai, Yuting Tang, Xin Cavener, Douglas R. Mol Brain Research PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that PERK regulates Ca(2+) dynamics in insulin-secreting β-cells underlying glucose-stimulated insulin secretion, and modulates Ca(2+) signals-dependent working memory, we explored the role of PERK in regulating G(q) protein-coupled Ca(2+) dynamics in pyramidal neurons. We found that acute PERK inhibition by the use of a highly specific PERK inhibitor reduced the intracellular Ca(2+) rise stimulated by the activation of acetylcholine, metabotropic glutamate and bradykinin-2 receptors in primary cortical neurons. More specifically, acute PERK inhibition increased IP(3) receptor mediated ER Ca(2+) release, but decreased receptor-operated extracellular Ca(2+) influx. Impaired G(q) protein-coupled intracellular Ca(2+) rise was also observed in genetic Perk knockout neurons. Taken together, our findings reveal a novel role of PERK in neurons, which is eIF2α-independent, and suggest that the impaired working memory in forebrain-specific Perk knockout mice may stem from altered G(q) protein-coupled intracellular Ca(2+) dynamics in cortical pyramidal neurons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-016-0268-5) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-01 /pmc/articles/PMC5045583/ /pubmed/27716400 http://dx.doi.org/10.1186/s13041-016-0268-5 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhu, Siying McGrath, Barbara C. Bai, Yuting Tang, Xin Cavener, Douglas R. PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons |
title | PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons |
title_full | PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons |
title_fullStr | PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons |
title_full_unstemmed | PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons |
title_short | PERK regulates G(q) protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons |
title_sort | perk regulates g(q) protein-coupled intracellular ca(2+) dynamics in primary cortical neurons |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045583/ https://www.ncbi.nlm.nih.gov/pubmed/27716400 http://dx.doi.org/10.1186/s13041-016-0268-5 |
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