| Autor: |
Uematsu K; Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, Japan., Futter M, Hsieh-Wilson LC, Higashi H, Maeda H, Nairn AC, Greengard P, Nishi A |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neurochemistry [J Neurochem] 2005 Dec; Vol. 95 (6), pp. 1642-52. Date of Electronic Publication: 2005 Nov 21. |
| DOI: |
10.1111/j.1471-4159.2005.03491.x |
| Abstrakt: |
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 A 2A 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 A 2A 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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