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Studies on the molecular mechanism of calcium signaling and the role of IP3 receptor in development and differentiation

钙信号分子机制及IP3受体在发育分化中的作用研究

基本信息

批准号：
09308030
负责人：
MIKOSHIBA Katsuhiko
金额：
$ 18.37万
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：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The inositol 1,4,5-triaphosphate (IP3) receptor (IP3R) acts as a Ca2+ release channel on internal Ca2+ stores. Type 1 IP3R(IP3R1) is enriched in growth cones of neurons in chick dorsal root ganglia. Depletion in internal Ca2+ stores and inhibition of IP3 signaling with drugs inhibited neurite extension. Microinjection of heparin, a competitive IP3R blocker, induced neurite retraction. Acute localized loss of function of IP3R1 in the growth cone induced by chromophore assisted laser inactivation resulted in growth cones arrest and neurite retraction. IP3-induced Ca2+ release in growth cones appears to have a crucial role in control of nerve growth.Changes in [Ca2+]i are an essential factor regulating egg activation. Matured ascidian eggs are arrested at metaphase I , and two series of [Ca2+]i transients have been observed after fertilization : Ca2+ waves just fertilization (Series I) and [Ca2+]i oscillation between the first and second polar body extrusion (Series II). We investigated mechanisms involved in the elevation of [Ca2+]i and the role of the [Ca2+]i transients during egg activation in Ciona savignyi. The monoclonal antibody 18A10 against IP3 receptor type 1, which inhibits IP3-induced Ca2+ release in hamster and mouse eggs, did not show substantial inhibitory effects on series I or egg deformation, whereas Series II and the first cell division were inhibited by the antibody. Ruthenium red, an inhibitor of ryanodine receptor-mediated Ca2+ release, had no apparent effect of [Ca2+]i transients and other events related to the egg activation.

肌醇1，4，5-三磷酸（IP 3）受体（IP 3R）作为Ca 2+释放通道对内部Ca 2+储存起作用。1型IP 3R（IP 3R 1）在鸡背根神经节神经元的生长锥中富集。耗尽内部Ca 2+商店和抑制IP 3信号与药物抑制神经突起的延伸。微量注射竞争性IP 3R阻断剂肝素诱导神经突起回缩。发色团辅助激光失活诱导生长锥中IP 3 R1功能的急性局部丧失导致生长锥停滞和神经突回缩。IP 3诱导的生长锥内Ca ~（2+）释放在控制神经生长中起着重要作用，[Ca ~（2+）]i的变化是调节卵激活的重要因素。成熟的海鞘卵在中期I被捕获，受精后观察到两个系列的[Ca 2 +]i瞬变：受精时的Ca 2+波（系列I）和第一极体和第二极体排出之间的[Ca 2 +]i振荡（系列II）。我们调查的机制涉及的[Ca 2 +]i的升高和[Ca 2 +]i瞬变过程中的作用，在玻璃海鞘卵激活。单克隆抗体18 A10对IP 3受体1型，抑制IP 3诱导的钙释放在仓鼠和小鼠卵，没有表现出实质性的抑制作用系列I或卵变形，而系列II和第一次细胞分裂被抑制的抗体。钌红，Ryanodine受体介导的Ca 2+释放的抑制剂，没有明显的效果[Ca 2 +]i瞬变和其他事件相关的卵激活。