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 Pa...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2011-08-01
|
| Series: | Frontiers in Neuroanatomy |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnana.2011.00050/full |
| _version_ | 1818351738366722048 |
|---|---|
| author | Sven I Walaas Hugh Caroll Hemmings Paul eGreengard Angus Clark Nairn |
| author_facet | Sven I Walaas Hugh Caroll Hemmings Paul eGreengard Angus Clark Nairn |
| author_sort | Sven I Walaas |
| collection | DOAJ |
| 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 DARPP-32, RCS (Regulator of Calmodulin Signaling) 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. |
| first_indexed | 2024-12-13T18:42:31Z |
| format | Article |
| id | doaj.art-0c03b2b8fbc74fd887c3cd6b958b59ba |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-12-13T18:42:31Z |
| publishDate | 2011-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-0c03b2b8fbc74fd887c3cd6b958b59ba2022-12-21T23:35:10ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292011-08-01510.3389/fnana.2011.0005011374Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein PhosphatasesSven I Walaas0Hugh Caroll Hemmings1Paul eGreengard2Angus Clark Nairn3University of OsloWeill Medical College of Cornell UniversityRockefeller UniversityYale University School of MedicineDopamine 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 DARPP-32, RCS (Regulator of Calmodulin Signaling) 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.http://journal.frontiersin.org/Journal/10.3389/fnana.2011.00050/fullCalcineurinPhosphorylationProtein PhosphataseARPP-16ARPP-21DARPP-32 |
| spellingShingle | Sven I Walaas Hugh Caroll Hemmings Paul eGreengard Angus Clark Nairn Beyond the Dopamine Receptor: Regulation and Roles of Serine/Threonine Protein Phosphatases Frontiers in Neuroanatomy Calcineurin Phosphorylation Protein Phosphatase ARPP-16 ARPP-21 DARPP-32 |
| 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 | Calcineurin Phosphorylation Protein Phosphatase ARPP-16 ARPP-21 DARPP-32 |
| url | http://journal.frontiersin.org/Journal/10.3389/fnana.2011.00050/full |
| work_keys_str_mv | AT sveniwalaas beyondthedopaminereceptorregulationandrolesofserinethreonineproteinphosphatases AT hughcarollhemmings beyondthedopaminereceptorregulationandrolesofserinethreonineproteinphosphatases AT paulegreengard beyondthedopaminereceptorregulationandrolesofserinethreonineproteinphosphatases AT angusclarknairn beyondthedopaminereceptorregulationandrolesofserinethreonineproteinphosphatases |