| Project/Area Number |
02101001
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo (1992-1994)
Osaka University (1990-1991) |
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Principal Investigator |
MIKOSHIBA Katsuhiko Institute of Medical Science, University of Tokyo Professor, 医科学研究所, 教授 (30051840)
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| Co-Investigator(Kenkyū-buntansha) |
HIROSAWA Kazushige Institute of Medical Science, University of Tokyo Professor, 医科学研究所・, 教授 (30009980)
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| Project Period (FY) |
1990 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥252,000,000 (Direct Cost: ¥252,000,000)
Fiscal Year 1994: ¥41,000,000 (Direct Cost: ¥41,000,000)
Fiscal Year 1993: ¥55,000,000 (Direct Cost: ¥55,000,000)
Fiscal Year 1992: ¥41,000,000 (Direct Cost: ¥41,000,000)
Fiscal Year 1991: ¥45,000,000 (Direct Cost: ¥45,000,000)
Fiscal Year 1990: ¥70,000,000 (Direct Cost: ¥70,000,000)
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| Keywords | Ca^<2+> signaling / IP_3 receptor / endoplasmic reticulum / inositol 1,4,5-trisphosphate (IP_3) / Ca^<2+> channel / cerebellar mutant mouse / hippocampal neuron / Purkinje cell / イノシトール3リン酸レセブター / カルシュウムチャネル / アルツハイマー病 / IP3レセプタ- / カルシウム / IP3 / カルシウム放出能 / IP3(イノシトール3リン酸)レセプター / Ca^<2+>放出 / 受精現象 / Ca^<2+>波 / Ca^<2+>振動 / IP3(イノシトール3リン酸) / Ca^<2+>チャネル / 卵の活性化 / イノシト-ル3リン酸(IP_3) / イノシト-ル3リン酸(IP_3)レセプタ- / 滑面小胞体 / 人工脂質二重膜 / 細胞内膜系 |
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| Research Abstract |
Inositol 1,4,5-trisphosphate (InsP_3) is a second messenger which induces calcium release from the intracellular store sites. This InsP_3-induced calcium release (IICR) is mediated by an intracellular calcium release channel, InsP_3 receptor (InsP_3R). We have cloned the cDNAs of three different types of InsP_3R (types 1,2and3) so far, and have also found various alternatively-spliced variants of type 1 (neuronal type). The basic structure of all InsP_3R types is composed of three functional domains ; the ligand-binding domain (N-terminal portion) ; the modulatory domain (middle portion) which contains various sites for modulator-binding (ATP,calmodulin, Ca^<2+>, etc.) and phosphorylation (PKA,PKC,CaMKII) ; the channel domain (C-terminal portion) which contains six membrane-spanning segments and one putative "pore" -forming segment as the ion channel superfamily including voltage-sensitive and nucleotide-gated channels. InsP_3R forms a tetramer complex, so that each InsP_3-gated ion channel can have four ligand-binding sites. Our data indicate that each member of the InsP_3R family is differentially expressed in various cell-types, and in some cell-types can form heteromeric InsP_3R channels by assembling with the other receptor types. These results suggest that intracellular calcium signaling mediated by IICR in each cell-type is differently regulated. Thus, we recently have characterized the IICR activity of sole InsP_3R type by using the type-specifically purified receptor reconstituted in liposomes. We found that phosphorylation of type 1 receptor enhances IICR activity. We have also characterized the function role of the type 1 InsP_3R in some cell signalings by using the specific antibody as a channel blocker for the type 1 InsP_3R-mediated IICR.Calcium waves and oscillations in hamster eggs were clearly blocked. Introduction of the antisense nucleotide of the cDNA of Xenopus IP_3R which we cloned, into Xenopus eggs suppressed the egg activation.
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