Molecular Mechanism of corticohistoqenesis of the brain

大脑皮质组织发生的分子机制

• 批准号: 10044245
• 负责人: MIKOSHIBA Katsuhiko
• 金额: $ 5.63万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044245/
• 关键词: reelin; CR-50 antibody; cerebral cortex; cortex; 大脳; リーラー; CR50モノクローナル抗体; リーラーマウス; 小脳; プルキンエ細胞; 海馬; ニューロン

Reelin is a key mediator of ordered neuronal alignment in the brain. Here we demonstrate that Reelin molecules assemble each other to forms a huge protein complex both in vitro and in vivo. The Reelin-Reelin interaction is clearly inhibited by the function-blocking anti-Reelin antibody, CR-50, at a concentration known to inhibit Reelin function. This assembly is mediated by electrostatic interaction via the α-helix domains in the CR-50 epitope region. Recombinant CR-50 epitope fragments spontaneously constitute a soluble, string-like homopolymer with a regularly repeated structure composed of more than 40 monomers. These data suggest that Reelin exerts its biological function by composing a large protein assembly driven by the CR-50 epitope region, proposing a novel model of the Reelin signaling in neurodevelopment.

Reelin是大脑中有序神经元排列的关键介质。在这里，我们证明了Reelin分子在体外和体内相互组装形成一个巨大的蛋白质复合物。在已知抑制Reelin功能的浓度下，功能阻断抗Reelin抗体CR-50明显抑制Reelin-Reelin相互作用。该组装通过CR-50表位区中的α-螺旋结构域的静电相互作用介导。重组CR-50表位片段自发地构成可溶性的线状均聚物，其具有由40多个单体组成的规则重复结构。这些数据表明，Reelin通过组成由CR-50表位区驱动的大蛋白组装体来发挥其生物学功能，提出了Reelin信号传导在神经发育中的新模型。

项目成果

Sato,Y.et.al.: "Adenophostin,a potent agonist of the inositol 1,4,5-trisphosphate receptor,is useful for fertilization of mouse oocytes injected with round spermatids leading to normal offspring" Biology of Reproduction. 58. 867-873 (1998)

Sato，Y.et.al.：“腺磷蛋白是肌醇 1,4,5-三磷酸受体的有效激动剂，可用于注射圆形精子细胞的小鼠卵母细胞受精，从而产生正常后代”《生殖生物学》。

Yoshikawa, F. et al.: "Cooperative formation of the ligand-binding site of the inositol"J.Biol.Chem.. 274. 328-334 (1999)

Yoshikawa, F.等人：“肌醇配体结合位点的协同形成”J.Biol.Chem.. 274. 328-334 (1999)

Muto,A.et.al.: "Activation of inositol 1,4,5-trisphosphate receptors induces transient changes in cell shape of fertilized Xenopus eggs." Cell Motility and the Cytoskeleton. 39. 201-208 (1998)

Muto,A.et.al.：“肌醇 1,4,5-三磷酸受体的激活会引起非洲爪蟾受精卵细胞形状的短暂变化。”

Baylis, H. A.. Et al: "Inositol 1,4,5-trisphospate receptors are strongly expressed"J. Mol.Biol.. 294. 467-476 (1999)

Baylis, H. A.. 等人：“肌醇 1,4,5-三磷酸受体强烈表达”J.

Nagata, E., Tanaka, K., Suzuki, S., Dembo, T., Fukuuchi, Y., Futatsugi, A. and Mikoshiba, K.: "Selective inhibition of inostitol 1, 4, 5-trisphosphate-induced Ca2+ release in the CA1 region of the hippocampus in the ischemic gerbil."Neuroscience. 93. 995-

Nagata, E.、Tanaka, K.、Suzuki, S.、Dembo, T.、Fukuuchi, Y.、Futatsugi, A. 和 Mikoshiba, K.：“选择性抑制肌醇 1, 4, 5-三磷酸诱导的 Ca2+