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KAKEN_16K07075seika.pdf
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Title |
Title |
IRBITファミリーによるpH・塩素イオン濃度制御が神経機能に果たす役割の解明
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Kana |
IRBIT ファミリー ニ ヨル pH・エンソ イオン ノウド セイギョ ガ シンケイ キノウ ニ ハタス ヤクワリ ノ カイメイ
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IRBIT famirī ni yoru pH enso ion nōdo seigyo ga shinkei kinō ni hatasu yakuwari no kaimei
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Regulation of intracellular pH and chloride changes by IRBIT family in neurons
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河合, 克宏
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カワアイ, カツヒロ
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Kawaai, Katsuhiro
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慶應義塾大学・医学部 (信濃町) ・助教
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Research team head
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科研費研究者番号 : 00553653
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2019
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科学研究費補助金研究成果報告書
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2018
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IRBITファミリーのpHおよび塩素イオン濃度制御に関与する新規相互分子を同定し、機能解析を行った。その結果、IRBITファミリーはAnion Exchanger 2/3およびAno1と相互作用し、その活性を制御することを明らかにした。IRBIT欠損神経細胞はpHおよび塩素イオン濃度変化に異常がある事がわかった。IRBITファミリーは様々な標的分子と結合する多機能性タンパク質であることから、IRBITファミリーの標的分子選択性に関して解析を行い、IRBITおよびLongIRBITのsplicing variantsは異なる発現分布、タンパク質安定性、標的分子親和性を示すことを明らかにした。
We identified anion exchanger (AE) and calcium dependent chloride channel (CaCC) as novel IRBIT family interacting molecule and found that IRBIT family regulates the activity of AE and CaCC. IRBIT, Long-IRBIT, AE, and CaCC were expressed in hippocampal neurons. We also found that the intracellular pH and chloride changes were impaired in hippocampal neurons, which were derived from IRBIT or Long-IRBIT knockout mouse. In addition, we found that IRBIT and Long-IRBIT splicing variants formed heteromultimers and N-terminal variation of Long-IRBIT by splicing affected protein stability and target selectivity. Thus, N-terminal variation of IRBIT family members mediates the regulation of multiple signaling pathways.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2016~2018
課題番号 : 16K07075
研究分野 : 神経化学
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