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STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit
N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosin...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114553/ https://www.ncbi.nlm.nih.gov/pubmed/27857196 http://dx.doi.org/10.1038/srep36684 |
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author | Tian, Meng Xu, Jian Lei, Gang Lombroso, Paul J. Jackson, Michael F. MacDonald, John F. |
author_facet | Tian, Meng Xu, Jian Lei, Gang Lombroso, Paul J. Jackson, Michael F. MacDonald, John F. |
author_sort | Tian, Meng |
collection | PubMed |
description | N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gα(q)-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP(3)Rs and can depress NMDA-evoked currents with modest intracellular Ca(2+) buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca(2+) buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca(2+) dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation. |
format | Online Article Text |
id | pubmed-5114553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51145532016-11-25 STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit Tian, Meng Xu, Jian Lei, Gang Lombroso, Paul J. Jackson, Michael F. MacDonald, John F. Sci Rep Article N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gα(q)-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP(3)Rs and can depress NMDA-evoked currents with modest intracellular Ca(2+) buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca(2+) buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca(2+) dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation. Nature Publishing Group 2016-11-18 /pmc/articles/PMC5114553/ /pubmed/27857196 http://dx.doi.org/10.1038/srep36684 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Tian, Meng Xu, Jian Lei, Gang Lombroso, Paul J. Jackson, Michael F. MacDonald, John F. STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit |
title | STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit |
title_full | STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit |
title_fullStr | STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit |
title_full_unstemmed | STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit |
title_short | STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit |
title_sort | step activation by gαq coupled gpcrs opposes src regulation of nmda receptors containing the glun2a subunit |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114553/ https://www.ncbi.nlm.nih.gov/pubmed/27857196 http://dx.doi.org/10.1038/srep36684 |
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