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Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases

Dopamine plays an important modulatory role in the central nervous system, helping to control critical aspects of motor function and reward learning. Alteration in normal dopaminergic neurotransmission underlies multiple neurological diseases including schizophrenia, Huntington’s disease, and Parkin...

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Autores principales: Walaas, Sven Ivar, Hemmings, Hugh Caroll, Greengard, Paul, Nairn, Angus Clark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162284/
https://www.ncbi.nlm.nih.gov/pubmed/21904525
http://dx.doi.org/10.3389/fnana.2011.00050
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author Walaas, Sven Ivar
Hemmings, Hugh Caroll
Greengard, Paul
Nairn, Angus Clark
author_facet Walaas, Sven Ivar
Hemmings, Hugh Caroll
Greengard, Paul
Nairn, Angus Clark
author_sort Walaas, Sven Ivar
collection PubMed
description Dopamine plays an important modulatory role in the central nervous system, helping to control critical aspects of motor function and reward learning. Alteration in normal dopaminergic neurotransmission underlies multiple neurological diseases including schizophrenia, Huntington’s disease, and Parkinson’s disease. Modulation of dopamine-regulated signaling pathways is also important in the addictive actions of most drugs of abuse. Our studies over the last 30 years have focused on the molecular actions of dopamine acting on medium spiny neurons, the predominant neurons of the neostriatum. Striatum-enriched phosphoproteins, particularly dopamine and adenosine 3′:5′-monophosphate-regulated phosphoprotein of 32 kDa (DARPP-32), regulator of calmodulin signaling (RCS), and ARPP-16, mediate pleiotropic actions of dopamine. Notably, each of these proteins, either directly or indirectly, regulates the activity of one of the three major subclasses of serine/threonine protein phosphatases, PP1, PP2B, and PP2A, respectively. For example, phosphorylation of DARPP-32 at Thr34 by protein kinase A results in potent inhibition of PP1, leading to potentiation of dopaminergic signaling at multiple steps from the dopamine receptor to the nucleus. The discovery of DARPP-32 and its emergence as a critical molecular integrator of striatal signaling will be discussed, as will more recent studies that highlight novel roles for RCS and ARPP-16 in dopamine-regulated striatal signaling pathways.
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spelling pubmed-31622842011-09-08 Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases Walaas, Sven Ivar Hemmings, Hugh Caroll Greengard, Paul Nairn, Angus Clark Front Neuroanat Neuroscience Dopamine plays an important modulatory role in the central nervous system, helping to control critical aspects of motor function and reward learning. Alteration in normal dopaminergic neurotransmission underlies multiple neurological diseases including schizophrenia, Huntington’s disease, and Parkinson’s disease. Modulation of dopamine-regulated signaling pathways is also important in the addictive actions of most drugs of abuse. Our studies over the last 30 years have focused on the molecular actions of dopamine acting on medium spiny neurons, the predominant neurons of the neostriatum. Striatum-enriched phosphoproteins, particularly dopamine and adenosine 3′:5′-monophosphate-regulated phosphoprotein of 32 kDa (DARPP-32), regulator of calmodulin signaling (RCS), and ARPP-16, mediate pleiotropic actions of dopamine. Notably, each of these proteins, either directly or indirectly, regulates the activity of one of the three major subclasses of serine/threonine protein phosphatases, PP1, PP2B, and PP2A, respectively. For example, phosphorylation of DARPP-32 at Thr34 by protein kinase A results in potent inhibition of PP1, leading to potentiation of dopaminergic signaling at multiple steps from the dopamine receptor to the nucleus. The discovery of DARPP-32 and its emergence as a critical molecular integrator of striatal signaling will be discussed, as will more recent studies that highlight novel roles for RCS and ARPP-16 in dopamine-regulated striatal signaling pathways. Frontiers Research Foundation 2011-08-26 /pmc/articles/PMC3162284/ /pubmed/21904525 http://dx.doi.org/10.3389/fnana.2011.00050 Text en Copyright © 2011 Walaas, Hemmings, Greengard and Nairn. http://www.frontiersin.org/licenseagreement This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.
spellingShingle Neuroscience
Walaas, Sven Ivar
Hemmings, Hugh Caroll
Greengard, Paul
Nairn, Angus Clark
Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases
title Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases
title_full Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases
title_fullStr Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases
title_full_unstemmed Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases
title_short Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases
title_sort beyond the dopamine receptor: regulation and roles of serine/threonine protein phosphatases
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162284/
https://www.ncbi.nlm.nih.gov/pubmed/21904525
http://dx.doi.org/10.3389/fnana.2011.00050
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