Phosholipase C-related inactive protein is involved in trafficking of γ2 subunit-containing GABAA receptors to the cell surface

Akiko Mizokami, Takashi Kanematsu, Hitoshi Ishibashi, Taku Yamaguchi, Isei Tanida, Kei Takenaka, Keiichi Nakayama, Kiyoko Fukami, Tadaomi Takenawa, Eiki Kominami, Stephen J. Moss, Tsuneyuki Yamamoto, Junichi Nabekura, Masato Hirata

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Abstract

The subunit composition of GABAA receptors is known to be associated with distinct physiological and pharmacological properties. Previous studies that used phospholipase C-related inactive protein type 1 knock-out (PRIP-1 KO) mice revealed that PRIP-1 is involved in the assembly and/or the trafficking of γ2 subunit-containing GABAA receptors. There are two PRIP genes in mammals; thus the roles of PRIP-1 might be compensated partly by those of PRIP-2 in PRIP-1 KO mice. Here we used PRIP-1 and PRIP-2 double knock-out (PRIP-DKO) mice and examined the roles for PRIP in regulating the trafficking of GABAA receptors. Consistent with previous results, sensitivity to diazepam was reduced in electrophysiological and behavioral analyses of PRIP-DKO mice, suggesting an alteration of γ2 subunit-containing GABAA receptors. The surface numbers of diazepam binding sites (α/γ2 subunits) assessed by [3H]flumazenil binding were reduced in the PRIP-DKO mice as compared with those of wild-type mice, whereas the cell surface GABA binding sites (α/β subunits, assessed by [3H]muscimol binding) were increased in PRIP-DKO mice. The association between GABAA receptors and GABAA receptor-associated protein (GABARAP) was reduced significantly in PRIP-DKO neurons. Disruption of the direct interaction between PRIP and GABAA receptor β subunits via the use of a peptide corresponding to the PRIP-1 binding site reduced the cell surface expression of γ2 subunit-containing GABAA receptors in cultured cell lines and neurons. These results suggest that PRIP is implicated in the trafficking of γ2 subunit-containing GABAA receptors to the cell surface, probably by acting as a bridging molecule between GABARAP and the receptors.

Original languageEnglish
Pages (from-to)1692-1701
Number of pages10
JournalJournal of Neuroscience
Volume27
Issue number7
DOIs
Publication statusPublished - Feb 14 2007

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GABA-A Receptors
Knockout Mice
Proteins
Binding Sites
Type C Phospholipases
Diazepam
Neurons
Flumazenil
Muscimol
gamma-Aminobutyric Acid
Mammals
Cultured Cells
Pharmacology
Cell Line
Peptides

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Phosholipase C-related inactive protein is involved in trafficking of γ2 subunit-containing GABAA receptors to the cell surface. / Mizokami, Akiko; Kanematsu, Takashi; Ishibashi, Hitoshi; Yamaguchi, Taku; Tanida, Isei; Takenaka, Kei; Nakayama, Keiichi; Fukami, Kiyoko; Takenawa, Tadaomi; Kominami, Eiki; Moss, Stephen J.; Yamamoto, Tsuneyuki; Nabekura, Junichi; Hirata, Masato.

In: Journal of Neuroscience, Vol. 27, No. 7, 14.02.2007, p. 1692-1701.

Research output: Contribution to journalArticle

Mizokami, A, Kanematsu, T, Ishibashi, H, Yamaguchi, T, Tanida, I, Takenaka, K, Nakayama, K, Fukami, K, Takenawa, T, Kominami, E, Moss, SJ, Yamamoto, T, Nabekura, J & Hirata, M 2007, 'Phosholipase C-related inactive protein is involved in trafficking of γ2 subunit-containing GABAA receptors to the cell surface', Journal of Neuroscience, vol. 27, no. 7, pp. 1692-1701. https://doi.org/10.1523/JNEUROSCI.3155-06.2007
Mizokami, Akiko ; Kanematsu, Takashi ; Ishibashi, Hitoshi ; Yamaguchi, Taku ; Tanida, Isei ; Takenaka, Kei ; Nakayama, Keiichi ; Fukami, Kiyoko ; Takenawa, Tadaomi ; Kominami, Eiki ; Moss, Stephen J. ; Yamamoto, Tsuneyuki ; Nabekura, Junichi ; Hirata, Masato. / Phosholipase C-related inactive protein is involved in trafficking of γ2 subunit-containing GABAA receptors to the cell surface. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 7. pp. 1692-1701.
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