title: Phospholipase C-related but catalytically inactive protein is required for insulin-induced cell surface expression of gamma-aminobutyric acid type A receptors.
abstract: The gamma-aminobutyric acid type A (GABA(A)) receptors play a pivotal role in fast synaptic inhibition in the central nervous system. One of the key factors for determining synaptic strength is the number of receptors on the postsynaptic membrane, which is maintained by the balance between cell surface insertion and endocytosis of the receptors. In this study, we investigated whether phospholipase C-related but catalytically inactive protein (PRIP) is involved in insulin-induced GABA(A) receptor insertion. Insulin potentiated the GABA-induced Cl(-) current (I(GABA)) by about 30% in wild-type neurons, but not in PRIP1 and PRIP2 double-knock-out (DKO) neurons, suggesting that PRIP is involved in insulin-induced potentiation. The phosphorylation level of the GABA(A) receptor beta-subunit was increased by about 30% in the wild-type neurons but not in the mutant neurons, which were similar to the changes observed in I(GABA). We also revealed that PRIP recruited active Akt to the GABA(A) receptors by forming a ternary complex under insulin stimulation. The disruption of the binding between PRIP and the GABA(A) receptor beta-subunit by PRIP interference peptide attenuated the insulin potentiation of I(GABA). Taken together, these results suggest that PRIP is involved in insulin-induced GABA(A) receptor insertion by recruiting active Akt to the receptor complex.
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujii
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Fukami
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moss
authors.forename: Junichi
authors.initials: J
authors.lastname: Nabekura
authors.forename: Masato
authors.initials: M
authors.lastname: Hirata
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D047468:Immunoprecipitation; D007328:Insulin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002352:Carrier Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D019319:Okadaic Acid; D019869:Phosphatidylinositol 3-Kinases; D011963:Receptors, GABA-A; D000077191:Wortmannin; C513987:PRIP-1 phospholipase C-related protein, mouse