GABAA receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein

Miho Terunuma, Il Sung Jang, Sang Hoon Ha, Josef T. Kittler, Takashi Kanematsu, Jasmina N. Jovanovic, Keiichi I. Nakayama, Norio Akaike, Sung Ho Ryu, Stephen J. Moss, Masato Hirata

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

Abstract

GABAA 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 1α (PP1α) in facilitating GABAA receptor phospho-dependent regulation using PRIP-1-/- mice. In wild-type animals, robust phosphorylation and functional modulation of GABAA receptors containing β3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1-/- mice. PRIP-1-/- mice exhibited enhanced PP1α activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABAA receptor β subunits, and moreover, these proteins were found to be PP1α substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1α-PRIP-1 complexes, providing a local mechanism for the activation of PP1α. Together, these results suggest an essential role for PRIP-1 in controlling GABAA receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors.

Original languageEnglish
Pages (from-to)7074-7084
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number32
DOIs
Publication statusPublished - Aug 11 2004

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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