Role of IP_3 receptor/Ca^<2+> signaling in neural plasticity and brain development

IP_3受体/Ca^2信号在神经可塑性和大脑发育中的作用

• 批准号: 11308032
• 负责人: MIKOSHIBA Katsuhiko
• 金额: $ 23.04万
• 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 (A).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11308032/
• 关键词: IP_3; Ca^<2+>; endoplasmic reticulum; レーザー光; マラカイトグリーン; IP3; IP_3受容体; 神経成長円錐; LTD; LTP; 神経可塑性; レーザー; Ca^<2+>

We have found that wave and Ca2+ oscillation is produced through the Ca2+ channel localized on the endoplasmic reticulum which is a Ca2+ store site inside the cell, and not through Ca2+ channel on the plasma membrane.We used CALI(chromophore assisted laser inactivation)method using laser beam to study if IP3 receptor mediated Ca2+ movement is involved in growth cone formation and neurite extention. We used malakite green to label specific antibody against type 1 IP3 receptor. We added laser beam to the dye to produce redicals.While control antibody showed no block in neurite extention, antibody against type IP3 showed retraction of neurite, only when laser is added at growth cone.This suggests that IP3 receptor medited Ca2+ release is involved in neurite extention.

我们发现，波动和钙振荡是通过内质网上的钙离子通道产生的，内质网是细胞内的钙储存部位，而不是质膜上的钙通道。我们采用激光发色团辅助激光失活(CALI)的方法，研究了IP3受体介导的钙离子运动是否参与了生长锥的形成和轴突的伸展。我们用孔雀石绿标记了针对1型IP3受体的特异性抗体。我们在染料中加入激光产生修饰物，对照抗体对突起的伸展没有阻断，而抗IP3型抗体只有在生长锥体加入激光时才显示出突起的回缩，这表明IP3受体介导的钙释放参与了突起的伸展。

项目成果

Michikawa, T., et al: "Calmodulin mediates calcium-dependent inactivation of the cerebellar type 1 inositoll, 4,5-trisphosphate receptor."Neuron. 23. 799-808 (1999)

Michikawa, T. 等人：“钙调蛋白介导小脑 1 型肌醇 4,5-三磷酸受体的钙依赖性失活。”神经元。

Yoshikawa, F., et al: "Cooperative formation of the ligand-binding site of the inositol 1,4,5-triphosphate receptor by two separable domains."J.Biol.Chem.. 274. 328-334 (1999)

Yoshikawa, F., 等人：“通过两个可分离的结构域协同形成肌醇 1,4,5-三磷酸受体的配体结合位点。”J.Biol.Chem.. 274. 328-334 (1999)

Inoue, T., et al: "Type 1 inositol 1, 4, 5-trisphosphate receptor is required for induction of long-term depression in cerebellar Purkinje neurons."J.Neurosci.. 18. 5366-5373

Inoue, T., 等人：“1 型肌醇 1,4,5-三磷酸受体是诱导小脑浦肯野神经元长期抑制所必需的。”J.Neurosci.. 18. 5366-5373

Yoshikawa, F., et al: "Mutational analysis of the ligand binding site of the inositol 1, 4, 5-trisphosphate receptor."J.Biol.Chem.. 271. 18277-18284 (1996)

Yoshikawa, F., 等人：“肌醇 1,4,5-三磷酸受体配体结合位点的突变分析。”J.Biol.Chem.. 271. 18277-18284 (1996)

Fukuda,M.,: "Phospholipid composition dependenceCa^<2+>-dependent phospholipid binding to the C2A domain of synaptotagmin IV."J.Biol.Chem. 271. 8430-8434 (1996)

Fukuda，M.，：“磷脂组成依赖性Ca^2依赖性磷脂与突触结合蛋白IV的C2A结构域结合。”J.Biol.Chem。