Biochemical characterization of the IMPA2 gene product
| Project/Area Number |
16591175
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | RIKEN |
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Principal Investigator |
OHNISHI Tetsuo RIKEN, Laboratory for Molecular Psychiatry, Research Scientist, 分子精神科学研究チーム, 研究員 (80373281)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kazuo RIKEN, Laboratory for Molecular Psychiatry, Research Scientist, 分子精神科学研究チーム, 研究員 (10322695)
YOSHIKAWA Takeo RIKEN, Laboratory for Molecular Psychiatry, Head, 分子精神科学研究チーム, チームリーダー (30249958)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | bipolar disorder / lithium / inositol monophosphatase / schizophrenia / febrile seizures / inositol depletion hypothesis / mania / depression / IMPA2 / イノシトール / モデル動物 / IMPA1 / 躁うつ病 / イノシトールリン酸 |
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| Research Abstract |
Lithium is used in the clinical treatment of bipolar disorder, a disease where patients suffer mood swings between mania and depression. Although the mode of lithium's action remains elusive, a putative primary target is thought to be inositol monophosphatase (IMPase) activity. Two IMPase genes have been identified in mammals, the well characterized myo-inositol monophosphatase 1 (IMPA1) and myo-inositol monophosphatase 2 (IMPA2). Several lines of genetic evidence have implicated IMPA2 in the pathogenesis of not only bipolar disorder, but also schizophrenia and febrile seizures. However, little is known about the protein, although it is predicted to have lithium-inhibitable IMPase activity based on its high homology to IMPA1. Here we present the first biochemical study comparing the enzyme activity of IMPA2 with IMPA1. We demonstrate that IMPA2 forms homodimers in vivo but not heterodimers with IMPA1. Recombinant IMPA2 exhibits IMPase activity, although maximal activity requires higher concentrations of magnesium and a higher pH. IMPA2 shows significantly lower activity towards myo-inositol monophosphate than IMPA1. We therefore screened for additional substrates that could be more efficiently dephosphorylated by IMPA2, but failed to find any. Importantly, when using myo-inositol monophosphate as a substrate, the IMPase activity of IMPA2 was inhibited at high lithium and restricted magnesium concentrations, a kinetic that distinguishes it from IMPA1. Collectively, our data suggest that IMPA2 has a separate function in vivo from that of IMPA1.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels.2005
Author(s)
Yamada K, Ohnishi T, Hashimoto K, Ohba H, Iwayama-Shigeno Y, Toyoshima M, Okuno A, Takao H, Toyota T, Minabe Y, Nakamura K, Shimizu E, Itokawa M, Mori N, Iyo M, Yoshikawa T
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Journal Title
Biol.Psychiatry 57
Pages: 1493-1503
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression.
Author(s)
Yamada K, Hattori E, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Takao H, Minabe Y, Nakatani N, Higuchi T, Detera-Wadleigh SD, Yoshikawa T
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Biol.Psychiatry (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Failure to support a genetic contribution of AKT1 polymorphisms and altered AKT signaling in schizophrenia.
Author(s)
Ide M, Ohnishi M, Murayama M, Matsumoto I, Yamada K, Iwayama Y, Irena D, Toyota T, Asada T, Takashima A, Yoshikawa T
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Description
「研究成果報告書概要(欧文)」より
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