A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation

Abstract Mechanical pain serves as a base clinical symptom for many of the world’s most debilitating syndromes. Ion channels expressed by peripheral sensory neurons largely contribute to mechanical hypersensitivity. Transient Receptor Potential A 1 (TRPA1) is a ligand-gated ion channel that contribu...

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Autores principales:	Allison Doyle Brackley, Ruben Gomez, Kristi A. Guerrero, Armen N. Akopian, Marc J. Glucksman, Junhui Du, Susan M. Carlton, Nathaniel A. Jeske
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78d62c56f9cc4d618d2eefe60eaa2041
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spelling	oai:doaj.org-article:78d62c56f9cc4d618d2eefe60eaa20412021-12-02T16:08:23ZA-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation10.1038/s41598-017-01999-42045-2322https://doaj.org/article/78d62c56f9cc4d618d2eefe60eaa20412017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01999-4https://doaj.org/toc/2045-2322Abstract Mechanical pain serves as a base clinical symptom for many of the world’s most debilitating syndromes. Ion channels expressed by peripheral sensory neurons largely contribute to mechanical hypersensitivity. Transient Receptor Potential A 1 (TRPA1) is a ligand-gated ion channel that contributes to inflammatory mechanical hypersensitivity, yet little is known as to the post-translational mechanism behind its somatosensitization. Here, we utilize biochemical, electrophysiological, and behavioral measures to demonstrate that metabotropic glutamate receptor-induced sensitization of TRPA1 nociceptors stimulates targeted modification of the receptor. Type 1 mGluR5 activation increases TRPA1 receptor agonist sensitivity in an AKA-dependent manner. As a scaffolding protein for Protein Kinases A and C (PKA and PKC, respectively), AKAP facilitates phosphorylation and sensitization of TRPA1 in ex vivo sensory neuronal preparations. Furthermore, hyperalgesic priming of mechanical hypersensitivity requires both TRPA1 and AKAP. Collectively, these results identify a novel AKAP-mediated biochemical mechanism that increases TRPA1 sensitivity in peripheral sensory neurons, and likely contributes to persistent mechanical hypersensitivity.Allison Doyle BrackleyRuben GomezKristi A. GuerreroArmen N. AkopianMarc J. GlucksmanJunhui DuSusan M. CarltonNathaniel A. JeskeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allison Doyle Brackley Ruben Gomez Kristi A. Guerrero Armen N. Akopian Marc J. Glucksman Junhui Du Susan M. Carlton Nathaniel A. Jeske A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation
description	Abstract Mechanical pain serves as a base clinical symptom for many of the world’s most debilitating syndromes. Ion channels expressed by peripheral sensory neurons largely contribute to mechanical hypersensitivity. Transient Receptor Potential A 1 (TRPA1) is a ligand-gated ion channel that contributes to inflammatory mechanical hypersensitivity, yet little is known as to the post-translational mechanism behind its somatosensitization. Here, we utilize biochemical, electrophysiological, and behavioral measures to demonstrate that metabotropic glutamate receptor-induced sensitization of TRPA1 nociceptors stimulates targeted modification of the receptor. Type 1 mGluR5 activation increases TRPA1 receptor agonist sensitivity in an AKA-dependent manner. As a scaffolding protein for Protein Kinases A and C (PKA and PKC, respectively), AKAP facilitates phosphorylation and sensitization of TRPA1 in ex vivo sensory neuronal preparations. Furthermore, hyperalgesic priming of mechanical hypersensitivity requires both TRPA1 and AKAP. Collectively, these results identify a novel AKAP-mediated biochemical mechanism that increases TRPA1 sensitivity in peripheral sensory neurons, and likely contributes to persistent mechanical hypersensitivity.
format	article
author	Allison Doyle Brackley Ruben Gomez Kristi A. Guerrero Armen N. Akopian Marc J. Glucksman Junhui Du Susan M. Carlton Nathaniel A. Jeske
author_facet	Allison Doyle Brackley Ruben Gomez Kristi A. Guerrero Armen N. Akopian Marc J. Glucksman Junhui Du Susan M. Carlton Nathaniel A. Jeske
author_sort	Allison Doyle Brackley
title	A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation
title_short	A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation
title_full	A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation
title_fullStr	A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation
title_full_unstemmed	A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation
title_sort	a-kinase anchoring protein 79/150 scaffolds transient receptor potential a 1 phosphorylation and sensitization by metabotropic glutamate receptor activation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/78d62c56f9cc4d618d2eefe60eaa2041
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A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation

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