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2014 Fiscal Year Final Research Report

Clarifying the role of IRBIT in the coupling regulation of intracellular pH and Ca2+ in astrocytes.

Research Project

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Project/Area Number 24590332
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionShowa Pharmaceutical University

Principal Investigator

MIZUTANI Akihiro  昭和薬科大学, 薬学部, 教授 (30242861)

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)
Project Period (FY) 2012-04-01 – 2015-03-31
KeywordsIRBIT / multiple phosphorylation / IP3R / NBCe1
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.

Free Research Field

神経生化学

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Published: 2016-06-03  

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