Analysis of the pathogenic mechanism for neuropsychiatric disease-like abnormal behavior in IRBIT knockout mouse

• Project/Area Number: 24700389
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: KAWAAI Katsuhiro 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (00553653)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IRBIT / 多動障害 / モノアミン / CaMKII / NBC1 / pH / DIA / 行動異常 / TH / リン酸化

Research Abstract

An IP3R binding protein termed IRBIT (IP3R binding protein released with inositol 1,4,5-trisphosphate) that interacts with the IP3 binding core domain of IP3R and regulate the IP3 sensitivity of IP3R. Recently, we identified calcium/calmodulin-dependent kinase II alpha (CaMKIIalpha) as an IRBIT binding protein. In this study, we investigated the effect of IRBIT deletion on the monoamine (dopamine and norepinephrine) synthesis and intracellular pH regulation to explain the function of IRBIT in the central nervous system. We found that IRBIT regulated the phosphoryaltion state of TH by CaMKIIalpha. In addition, IRBIT contributed the regulation of intracellular pH by NBC1 in the neuron and astrocyte.

Research Products

• [Journal Article] IRBIT: A regulator of ion channels and ion transporters (2014)
  • Author(s): Ando H, Kawaai K, Mikoshiba K
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Volume: 印刷中 Issue: 10 Pages: 2195-204
  • DOI: 10.1016/j.bbamcr.2014.01.031
  • Peer Reviewed
• [Journal Article] Irbit Mediates Synergy Between Ca2+ and cAMP Signaling Pathways During Epithelial Transport in Mice. (2013)
  • Author(s): Park S, Shcheynikov N, Hong JH, Zheng C, Suh SH, Kawaai K, Ando H, Mizutani A, Abe T, Kiyonari H, Seki G, Yule D, Mikoshiba K, Muallem S
  • Journal Title: Gastroenterology Volume: S0016-5085(13) Issue: 1 Pages: 232-241
  • DOI: 10.1053/j.gastro.2013.03.047
  • Peer Reviewed
• [Journal Article] Irbit Mediates Synergy Between Ca2+ and cAMP Signaling Pathways During Epithelial Transport in Mice. (2013)
  • Author(s): Park S, Shcheynikov N, Hong JH, Zheng C, Suh SH, Kawaai K, Ando H, Mizutani A, Abe T, Kiyonari H, Seki G, Yule D, Mikoshiba K, Muallem S.
  • Journal Title: Gastroenterology Volume: 13 Pages: 461-7
  • Peer Reviewed