PMID- 16754670 OWN - NLM STAT- MEDLINE DCOM- 20061016 LR - 20220331 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 281 IP - 31 DP - 2006 Aug 4 TI - Modulation of GABA(A) receptor phosphorylation and membrane trafficking by phospholipase C-related inactive protein/protein phosphatase 1 and 2A signaling complex underlying brain-derived neurotrophic factor-dependent regulation of GABAergic inhibition. PG - 22180-22189 LID - S0021-9258(19)47738-7 [pii] LID - 10.1074/jbc.M603118200 [doi] AB - Brain-derived neurotrophic factor (BDNF) modulates several distinct aspects of synaptic transmission, including GABAergic transmission. Exposure to BDNF alters properties of GABA(A) receptors and induces changes in the expression level at the cell surface. Although phospholipase C-related inactive protein-1 (PRIP-1) plays an important role in GABA(A) receptor trafficking and function, its role in BDNF-dependent modulation of these receptors, together with the role of PRIP-2, was investigated using neurons cultured from PRIP double knock-out mice. The BDNF-dependent inhibition of whole cell GABA-evoked currents observed in wild type neurons was not detected in neurons cultured from knock-out mice. Instead, a gradual increase in GABA-evoked currents in these neurons correlated with a gradual increase in phosphorylation of GABA(A) receptor beta3 subunit in response to BDNF. To characterize the specific role(s) that PRIP plays as components of underlying molecular machinery, we examined the recruitment of protein phosphatase(s) to GABA(A) receptors. We demonstrate that PRIP associates with phosphatases as well as with beta subunits. PRIP was found to colocalize with GABA(A) receptor clusters in cultured neurons and with recombinant GABA(A) receptors when co-expressed in HEK293 cells. Importantly, a peptide mimicking a domain of PRIP involved in binding to beta subunits disrupted the co-localization of these proteins in HEK293 cells and potently inhibited the BDNF-mediated attenuation of GABA(A) receptor currents in wild type neurons. Together, the results suggest that PRIP plays an important role in BDNF-dependent regulation of GABA(A) receptors by mediating the specific association between beta subunits of these receptors with protein phosphatases. FAU - Kanematsu, Takashi AU - Kanematsu T AD - Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan. FAU - Yasunaga, Atsushi AU - Yasunaga A AD - Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan. FAU - Mizoguchi, Yoshito AU - Mizoguchi Y AD - Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan; Department of Developmental Physiology, National Institute for Physiological Science, Okazaki 444-8585, Japan. FAU - Kuratani, Akiko AU - Kuratani A AD - Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan. FAU - Kittler, Josef T AU - Kittler JT AD - Department of Physiology, University College London, London WC1E 6BT, United Kingdom. FAU - Jovanovic, Jasmina N AU - Jovanovic JN AD - Department of Pharmacology, School of Pharmacy, Brunswick Square, London, WC1N 1AX, United Kingdom. FAU - Takenaka, Kei AU - Takenaka K AD - Department of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. FAU - Nakayama, Keiichi I AU - Nakayama KI AD - Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. FAU - Fukami, Kiyoko AU - Fukami K AD - Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan. FAU - Takenawa, Tadaomi AU - Takenawa T AD - Department of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. FAU - Moss, Stephen J AU - Moss SJ AD - Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104. FAU - Nabekura, Junichi AU - Nabekura J AD - Department of Developmental Physiology, National Institute for Physiological Science, Okazaki 444-8585, Japan. FAU - Hirata, Masato AU - Hirata M AD - Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: hirata1@dent.kyushu-u.ac.jp. LA - eng GR - G120/972/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060605 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carrier Proteins) RN - 0 (GABA Antagonists) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Multiprotein Complexes) RN - 0 (PRIP-1 phospholipase C-related protein, mouse) RN - 0 (Protein Subunits) RN - 0 (Receptors, GABA-A) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.16 (Protein Phosphatase 1) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*physiology MH - Carrier Proteins/metabolism/*physiology MH - Cell Line MH - Cell Membrane/*metabolism MH - Electrophysiology MH - *GABA Antagonists MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Mice MH - Mice, Knockout MH - Multiprotein Complexes/physiology MH - Neurons/chemistry/physiology MH - Phosphoprotein Phosphatases/metabolism/*physiology MH - Phosphorylation MH - Protein Phosphatase 1 MH - Protein Subunits/metabolism MH - Protein Transport MH - Receptors, GABA-A/*metabolism MH - *Signal Transduction EDAT- 2006/06/07 09:00 MHDA- 2006/10/17 09:00 CRDT- 2006/06/07 09:00 PHST- 2006/06/07 09:00 [pubmed] PHST- 2006/10/17 09:00 [medline] PHST- 2006/06/07 09:00 [entrez] AID - S0021-9258(19)47738-7 [pii] AID - 10.1074/jbc.M603118200 [doi] PST - ppublish SO - J Biol Chem. 2006 Aug 4;281(31):22180-22189. doi: 10.1074/jbc.M603118200. Epub 2006 Jun 5.