1994 Fiscal Year Final Research Report Summary
Moleculan mechanism of IP_3 receptor Ca^<2+> channel and the role of the receptor in signal transduction and growth and development
| 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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| 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 |
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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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Research Products
(12 results)
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[Publications] Miyawaki,A.,Furuichi,T.,Ryou,Y.,Yoshikawa,S.,Nakagawa,T.,Saitoh,T.&Mikoshiba,K.: "Structure-function relationship of the mouse inostiol 1,4,5-trisphosphate receptor." Proc.Natl.Acad.Sci.88. 4911-4915 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Nakagawa,T.,Okano,H.,Furuichi,T.,Aruga,J.&Mikoshiba,K.: "The subtypes of the mouse inositol 1,4,5-trisphosphate receptor are expressed in a tissue-specific and developmentally specific manner." Proc.Natl.Acad.Sci.88. 6244-6248 (1991)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyazaki,S.,Yuzaki,M.,Nakada,K.,Shirakawa,H.,Nakanishi,S.,Nakade,S.&Mikoshiba,K.: "Block of Ca^<2+> wave and Ca^<2+> oscillation by antibody to the inositol 1,4,5-trisphosphate receptor in fertilized hamster eggs." Science. 257. 251-255 (1992)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kume,S.,Muto,A.,Aruga,J.,Nakagawa,T.,Michikawa,T.,Furuichi,T.,Nakade,S.,Okano,H.& Mikoshiba,K.: "The xenopus IP_3 recepter:structure,function and localization in oocytes and egss." Cell. 73. 555-570 (1993)
Description
「研究成果報告書概要(和文)」より
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[Publications] Miyawaki, A., Furuichi, T., Ryou, Y., Yoshikawa, S., Nakagawa, T., Saitoh, T.& MIkoshiba, K.: "Structure-function relatonships of the mouse inositol 1,4,5-trisphosphate receptor." Proc.Natl.Acad.Sci.88. 4911-4915 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakagawa, T., Okano, H., Furuichi, T., Aruga, J.& Mikoshiba, K.: "The subtypes of the mouse inositol 1,4,5-trisphosphate receptor are expressed in a tissue-specific and developmentally specific manner." Proc.Natl.Acad.Sci.88. 6244-6248 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Miyazaki, S., Yuzaki, M., Nakada, K., Shirakawa, H., Nakanishi, S., Nakade, S.& Mikoshiba, K.: "Block of Ca2+ wave and Ca2+ oscillation by antibody to the inositol 1,4,5-trisphosphate receptor in fertilized hamster eggs." Science. 257. 251-255 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kume, S., Muto, A., Aruga, J., Nakagawa, T., Michikawa, T., Furuichi, T., Nakade, S., Okano, H.& Mikoshiba, K.: "The xenopus IP3 receptor : structure, function and localization in oocytes and eggs. H.& Mikoshiba, K." Cell. 73. 555-570 (1993)
Description
「研究成果報告書概要(欧文)」より
