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Regulation of spinophilin Ser94 phosphorylation in neostriatal neurons involves both DARPP-32-dependent and independent pathways

Uematsu, Ken and Futter, Marie and Hsieh-Wilson, Linda C. and Higashi, Hideho and Maeda, Hisao and Nairn, Angus C. and Greengard, Paul and Nishi, Akinori (2005) Regulation of spinophilin Ser94 phosphorylation in neostriatal neurons involves both DARPP-32-dependent and independent pathways. Journal of Neurochemistry, 95 (6). pp. 1642-1652. ISSN 0022-3042. doi:10.1111/j.1471-4159.2005.03491.x. https://resolver.caltech.edu/CaltechAUTHORS:20150519-160703348

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Abstract

Spinophilin is a protein phosphatase-1 (PP-1)- and actin-binding protein that is enriched in dendritic spines. Phosphorylation of the actin-binding domain of rat spinophilin at one or more sites by protein kinase A (PKA) inhibits actin binding. Here, we investigated the regulation of mouse spinophilin that contains only a single PKA-site (Ser94) within its actin-binding domain. In vitro phosphorylation of Ser94 resulted in the dissociation of spinophilin from actin filaments. In mouse neostriatal slices, phospho-Ser94 (p-Ser94) was dephosphorylated mainly by PP-1 and also by PP-2A. Activation of dopamine D1 receptors in striatonigral medium spiny neurons, and of adenosine A2A receptors in striatopallidal medium spiny neurons increased, whereas activation of dopamine D2 receptors in striatopallidal neurons decreased, spinophilin Ser94 phosphorylation. In neostriatal slices from DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) knockout mice, the effects of D1, D2 and A2A receptors were largely attenuated. Activation of NMDA receptors decreased Ser94 phosphorylation in a PP-2A-dependent, but DARPP-32-independent, manner. These results suggest that PKA-dependent phosphorylation of spinophilin at Ser94 in both striatonigral and striatopallidal neurons requires synergistic contributions from the PKA and DARPP-32/PP-1 pathways. In addition, PP-2A plays a role in Ser94 dephosphorylation in response to activation of both D2 and NMDA receptors.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1111/j.1471-4159.2005.03491.xDOIArticle
http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2005.03491.x/abstractPublisherArticle
ORCID:
AuthorORCID
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:© 2005 International Society for Neurochemistry. Issue published online: 21 NOV 2005; Article first published online: 21 NOV 2005; Received June 24, 2005; revised manuscript received August 9, 2005; accepted August 10, 2005. We thank Patrick B. Allen (Yale University School of Medicine, New Heaven, CT, USA) for providing the spinophilin antibody, and Yukako Terasaki, Keiko Fujisaki and Michiko Koga for excellent technical assistance. This research was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to AN) and grants from the USPHS (MH40899 and DA10044 to ACN and PG).
Funders:
Funding AgencyGrant Number
Japan Society for the Promotion of Science (JSPS)UNSPECIFIED
NIHMH40899
NIHDA10044
Subject Keywords:dopamine; glutamate; phosphorylation; spinophilin; striatum
Issue or Number:6
DOI:10.1111/j.1471-4159.2005.03491.x
Record Number:CaltechAUTHORS:20150519-160703348
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150519-160703348
Official Citation:Uematsu, K., Futter, M., Hsieh-Wilson, L. C., Higashi, H., Maeda, H., Nairn, A. C., Greengard, P. and Nishi, A. (2005), Regulation of spinophilin Ser94 phosphorylation in neostriatal neurons involves both DARPP-32-dependent and independent pathways. Journal of Neurochemistry, 95: 1642–1652. doi: 10.1111/j.1471-4159.2005.03491.x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:57677
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:19 May 2015 23:35
Last Modified:10 Nov 2021 21:53

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