Role of the PLC-related, catalytically inactive protein p130 in GABAA receptor function

Takashi Kanematsu, Il Sung Jang, Taku Yamaguchi, Hiroyasu Nagahama, Kenji Yoshimura, Kiyoshi Hidaka, Miho Matsuda, Hiroshi Takeuchi, Yoshio Misumi, Keiko Nakayama, Tsuneyuki Yamamoto, Norio Akaike, Masato Hirata, Kei Ichi Nakayama

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)

Abstract

The protein p130 was isolated from rat brain as an inositol 1, 4, 5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C-δ1 but lacking PLC activity. We show that p130 plays an important role in signaling by the type A receptor for γ-aminobutyric acid (GABA). Yeast two-hybrid screening identified GABARAP (GABAA receptor-associated protein), which is proposed to contribute to the sorting, targeting or clustering of GABAA receptors, as a protein that interacts with p130. Furthermore, p130 competitively inhibited the binding of the γ2 subunit of the GABAA receptor to GABARAP in vitro. Electrophysiological analysis revealed that the modulation of GABA-induced Cl-current by Zn2+ or diazepam, both of which act at GABAA receptors containing γ subunits, is impaired in hippocampal neurons of p130 knockout mice. Moreover, behavioral analysis revealed that motor coordination was impaired and the intraperitoneal injection of diazepam induced markedly reduced sedative and antianxiety effects in the mutant mice. These results indicate that p130 is essential for the function of GABAA receptors, especially in response to the agents acting on a γ2 subunit.

Original languageEnglish
Pages (from-to)1004-1011
Number of pages8
JournalEMBO Journal
Volume21
Issue number5
DOIs
Publication statusPublished - 2002 Mar 1
Externally publishedYes

Keywords

  • Diazepam
  • GABA
  • Knockout mice
  • P130

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Role of the PLC-related, catalytically inactive protein p130 in GABA<sub>A</sub> receptor function'. Together they form a unique fingerprint.

Cite this