2003 Fiscal Year Annual Research Report

神経可塑性及び脳の発生・分化におけるIP_3受容体/Ca^<2+>シグナリングの解析

Research Project

Project/Area Number	15100006
Research Institution	The University of Tokyo
Principal Investigator	御子柴克彦東京大学, 医科学研究所, 教授 (30051840)
Keywords	IP_3 / IP_3レセプター / カルシウム / IRBIT / 小胞体 / セカンドメッセンジャー / IP_3結合コアー
Research Abstract	IP_3レセプターに結合する多くのタンパク質がIP_3レセプターの制御に関わっている。IP_3レセプターに結合するタンパク質のうちIP_3で溶出される60kdのタンパク質IRBIT(IP_3 receptor binding protein released with inositol trisphosphate)を同定した。リン酸化されているとIP_3レセプターに結合し、脱リン酸化により離れる。IP_3によりIRBITの解離は生理的IP_3濃度で行われる。中枢神経系に多いが全ての臓器に広く存在する。IRBITはセカンドメッセンジャーのIP_3の三次メッセンジャーとして働く可能性やIP_3レセプターの転位等に関わっていることが考えられる。次にIP_3の結合がいかなる機構でカルシウムチャネルポアを開くか解析した。IP_3レセプターの各部位の欠失変異を作製してIP_3結合能とチャネル活性を調べたところ、N末端の1-223アミノ酸までの欠失の場合や、IP_3結合コア以降の細胞質部分の欠失とシステイン残基(2613番)の変異をおこすと、IP_3結合活性は保たれているが、チャネル活性は失われることを示した。以上の結果からIP_3結合の情報がIP_3結合コアーのN末端とC末端側の両サイドへ伝えられ、最後にIP_3レセプターのC末端側のシステイン残基を介してチャネルの開閉すると考えられる。さて従来、細胞内には小胞体が網状にはりめぐらされて、IP_3レセプターもそこに局在化しており、細胞内のさまざまな生理機能をひきおこすと考えられていた。本研究で網状小胞体の他にIP_3レセプターを含む顆粒状小胞体がチューブリンを介してキネシンモーターにより海馬内錐体細胞の樹状突起中を両方向性に高速移動していることを見いだした。しかも、この移動する顆粒小胞はカルシウムの取込みと放出能力を有した。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Mikoshiba, K., Zhang, S., Mizutani, A.: "Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized madin-darby canine kidney cells"J.Biol.Chem.. 278(6). 4048-4056 (2003)
[Publications] Ando, H., Mizutani, A., Matsu-ura, T., Mikoshiba, K.: "IRBIT, a novel inositol 1,4,5-trisphosphate (IP_3) receptor binding protein, is released from the IP_3 receptor upon IP_3 binding to the receptor"J.Biol.Chem.. 278. 10602-10612 (2003)
[Publications] Saneyoshi, T., Kume, S., Mikoshiba, K.: "Calcium/calmodulin-dependent protein kinase 1 inXenopus laevis"Comparative Biochemistry and Physiology. 134. 499-507 (2003)
[Publications] Yasuda, H., Higashi, H., Mikoshiba, K.: "Imaging of calcineurin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex"European Journal of Neuroscience. 17. 287-297 (2003)
[Publications] A., Inoue, T., Fujii, S., Kato, H., Mikoshiba, K.: "Long-term potentiation and long-term depression in hippocampal CA1 neurons of mice lacking the IP_3 type 1 receptor"Neuroscience. 117. 821-830 (2003)
[Publications] Uchida, K., Miyauchi, H., Furuichi, T., Michikawa, T., Mikoshiba, K: "Critical regions for activation gating of the inositol 1,4,5-Trisphosphate receptor"J.Biol.Chem.. 278(19). 16551-16560 (2003)
[Publications] M., Inoue, T., Kurosawa, M., Rafael A.F., Yoshida, N., Mikoshiba, K.: "Phospholipase Cδ4 is required for Ca^<2+> mobilization essential for acrosome reaction in sperm"J.Cell Biology. 161. 79-88 (2003)
[Publications] Hirota, J., Ando, H., Hamada, K., Mikoshiba, K: "Carbonic anhydrase-related protein is a novel binding protein for inositol 1,4,5-trisphosphate receptor type 1"Biochem.J.. 372. 435-441 (2003)
[Publications] Sandona D., Scolari, A., Mikoshiba, K., Volpe, P.: "Subcellular distribution of Homer 1b/c in relation to endoplasmic reticulum and plasma membrane proteins in Purkinje neurons"Neurochem Res.. 28(8). 1151-1158 (2003)
[Publications] Fujii, S., Mikoshiba, K., Kuroda, Y., Taufiq: "Cooperativity between activation of metabotropic glutamate receptors and NMDA receptors in the induction of LTP in hiprocampal CAl neurons"Neurosci.Res.. 46. 509-521 (2003)
[Publications] Kuruma, A., Inoue, T., Mikoshiba, K.: "Dynamics of Ca^<2+> and Na^+ in the dendrites of mouse cerebellar purkinje cells evoked by parallel fiber stimulation"Euro.J.Neurosci.. 18. 2677-2689 (2003)
[Publications] Hamada, K., Terauchi, A., Mikoshiba, K.: "Three-dimensional rearrangements within inositol 1,4,5-trisphosphate receptor by calcium"J.Bio.Chem.. 278(52). 52881-52889 (2003)
[Publications] Miyakawa-Naitou, A., Uhlen, P., Lal, M., Aizuman, O., Mikoshiba, K.: "Cell signaling microdomain with Na, K-ATPase and inositol 1,4,5-trisphate receptor generates calcium oscillations"J.Bio.Chem.. 278(50). 50355-50361 (2003)
[Publications] Hattori, M., Suzuki, A.Z., Nakamura, T., Inoue, T., Mikoshiba, K.: "Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca^<2+> signaling"J.Bio.Chem.. (in press). (2004)
[Publications] Iwai, M., Michikawa, T., Inoue, T., Mikoshiba, K.: "Kinesin dependent, rapid, bidirectional transport of ER sub-compartment in dendrites of neurons"J.Cell Sci.. 117. 163-175 (2004)
[Publications] Bannai, H., Iwai, M., Michikawa, T., Inoue, T., Mikoshiba, K.: "The regulatory domain of the inositol 1.4.5-trisphosphate receptor is necessary to maintain the channel domain closed - Possible physiological significance of specific cleavage by caspase-3"Biochem.J.. 377. 299-307 (2004)

2003 Fiscal Year Annual Research Report

神経可塑性及び脳の発生・分化におけるIP_3受容体/Ca^<2+>シグナリングの解析

Principal Investigator

御子柴 克彦 東京大学, 医科学研究所, 教授 (30051840)

Research Products

[Publications] Mikoshiba, K., Zhang, S., Mizutani, A.: "Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized madin-darby canine kidney cells"J.Biol.Chem.. 278(6). 4048-4056 (2003)

[Publications] Ando, H., Mizutani, A., Matsu-ura, T., Mikoshiba, K.: "IRBIT, a novel inositol 1,4,5-trisphosphate (IP_3) receptor binding protein, is released from the IP_3 receptor upon IP_3 binding to the receptor"J.Biol.Chem.. 278. 10602-10612 (2003)

[Publications] Saneyoshi, T., Kume, S., Mikoshiba, K.: "Calcium/calmodulin-dependent protein kinase 1 inXenopus laevis"Comparative Biochemistry and Physiology. 134. 499-507 (2003)

[Publications] Yasuda, H., Higashi, H., Mikoshiba, K.: "Imaging of calcineurin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex"European Journal of Neuroscience. 17. 287-297 (2003)

[Publications] A., Inoue, T., Fujii, S., Kato, H., Mikoshiba, K.: "Long-term potentiation and long-term depression in hippocampal CA1 neurons of mice lacking the IP_3 type 1 receptor"Neuroscience. 117. 821-830 (2003)

[Publications] Uchida, K., Miyauchi, H., Furuichi, T., Michikawa, T., Mikoshiba, K: "Critical regions for activation gating of the inositol 1,4,5-Trisphosphate receptor"J.Biol.Chem.. 278(19). 16551-16560 (2003)

[Publications] M., Inoue, T., Kurosawa, M., Rafael A.F., Yoshida, N., Mikoshiba, K.: "Phospholipase Cδ4 is required for Ca^<2+> mobilization essential for acrosome reaction in sperm"J.Cell Biology. 161. 79-88 (2003)

[Publications] Hirota, J., Ando, H., Hamada, K., Mikoshiba, K: "Carbonic anhydrase-related protein is a novel binding protein for inositol 1,4,5-trisphosphate receptor type 1"Biochem.J.. 372. 435-441 (2003)

[Publications] Sandona D., Scolari, A., Mikoshiba, K., Volpe, P.: "Subcellular distribution of Homer 1b/c in relation to endoplasmic reticulum and plasma membrane proteins in Purkinje neurons"Neurochem Res.. 28(8). 1151-1158 (2003)

[Publications] Fujii, S., Mikoshiba, K., Kuroda, Y., Taufiq: "Cooperativity between activation of metabotropic glutamate receptors and NMDA receptors in the induction of LTP in hiprocampal CAl neurons"Neurosci.Res.. 46. 509-521 (2003)

[Publications] Kuruma, A., Inoue, T., Mikoshiba, K.: "Dynamics of Ca^<2+> and Na^+ in the dendrites of mouse cerebellar purkinje cells evoked by parallel fiber stimulation"Euro.J.Neurosci.. 18. 2677-2689 (2003)

[Publications] Hamada, K., Terauchi, A., Mikoshiba, K.: "Three-dimensional rearrangements within inositol 1,4,5-trisphosphate receptor by calcium"J.Bio.Chem.. 278(52). 52881-52889 (2003)

[Publications] Miyakawa-Naitou, A., Uhlen, P., Lal, M., Aizuman, O., Mikoshiba, K.: "Cell signaling microdomain with Na, K-ATPase and inositol 1,4,5-trisphate receptor generates calcium oscillations"J.Bio.Chem.. 278(50). 50355-50361 (2003)

[Publications] Hattori, M., Suzuki, A.Z., Nakamura, T., Inoue, T., Mikoshiba, K.: "Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca^<2+> signaling"J.Bio.Chem.. (in press). (2004)

[Publications] Iwai, M., Michikawa, T., Inoue, T., Mikoshiba, K.: "Kinesin dependent, rapid, bidirectional transport of ER sub-compartment in dendrites of neurons"J.Cell Sci.. 117. 163-175 (2004)

御子柴克彦東京大学, 医科学研究所, 教授 (30051840)