Terunuma, M; Jang, IS; Ha, SH; Kittler, JT; Kanematsu, T; Jovanovic, JN; Nakayama, KI; ... Hirata, M; + view all Terunuma, M; Jang, IS; Ha, SH; Kittler, JT; Kanematsu, T; Jovanovic, JN; Nakayama, KI; Akaike, N; Ryu, SH; Moss, SJ; Hirata, M; - view fewer (2004) GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein. J NEUROSCI , 24 (32) 7074 - 7084. 10.1523/JNEUROSCI.1323-04.2004.

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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.

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