| Project/Area Number |
24590332
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SEKI Jouji 東京大学, 医学部附属病院, 講師 (30206619)
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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | IRBIT / multiple phosphorylation / IP3R / NBCe1 / 多重リン酸化 / 神経伝達 / 神経可塑性 / トリパータイトシナプス / 細胞内Ca2+シグナル / 細胞内pH / グリア細胞 |
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| Outline of Final Research Achievements |
IRBIT was in vitro phosphorylated by PKA on Ser62, Ser64, and Ser66, and the phosphorylations might be involved in the high affinity of high-phosphorylated IRBIT for IP3R. Indeed, IRBIT phosphorylated on Ser68, Ser71, Ser74 and Ser77 as well as on Ser62, Ser64,and Ser66 showed high-phosphorylated pattern revealed on Phos-Tag SDS-PAGE analysis. However, this densely phosphorylated IRBIT did not show high binding affinity to IP3R suggesting that additional phosphorylations on other sites or unidentified modifications are necessary for getting high affinity to IP3R.
In SLC4A4 deficient mice, an expression level of IRBIT protein was drastically reduced, and IRBIT in a soluble fraction was increased. Moreover, IRBIT was massively phosphorylated showing high affinity for IP3R. These results suggested that IRBIT was indeed phosphorylated in an NBCe1 activity dependent manner and could couple the intracellular pH homeostasis and Ca2+ dynamics.
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