GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein
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SCOPUS
- Title
- GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein
- Authors
- Terunuma, M; Jang, IS; Ha, SH; Kittler, JT; Kanematsu, T; Jovanovic, JN; Nakayama, KI; Akaike, N; Ryu, SH; Moss, SJ; Hirata, M
- Date Issued
- 2004-08-11
- Publisher
- SOC NEUROSCIENCE
- Abstract
- GABA(A) receptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates protein phosphatase 1alpha (PP1alpha) in facilitating GABA(A) receptor phospho-dependent regulation using PRIP-1(-/-) mice. In wild-type animals, robust phosphorylation and functional modulation of GABA(A) receptors containing beta3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1(-/-) mice. PRIP-1(-/-) mice exhibited enhanced PP1alpha activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABA(A) receptor beta subunits, and moreover, these proteins were found to be PP1alpha substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1alpha-PRIP-1 complexes, providing a local mechanism for the activation of PP1alpha. Together, these results suggest an essential role for PRIP-1 in controlling GABA(A) receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors.
- Keywords
- GABA; receptor; phosphorylation; phosphatase; protein kinase; cAMP; CELL-SURFACE EXPRESSION; 130 KDA PROTEIN; KINASE-C; FUNCTIONAL MODULATION; BETA SUBUNITS; A RECEPTORS; RAT-BRAIN; CATALYTIC SUBUNIT; PYRAMIDAL NEURONS; STRUCTURAL BASIS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17756
- DOI
- 10.1523/JNEUROSCI.1323-04.2004
- ISSN
- 0270-6474
- Article Type
- Article
- Citation
- JOURNAL OF NEUROSCIENCE, vol. 24, no. 32, page. 7074 - 7084, 2004-08-11
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