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

肌醇1，4，5-三磷酸(IP3)受体(IP3R)在体内钙库上起钙释放通道的作用。I型IP3R(IP3R1)富含于鸡背根神经节神经元的生长锥中。体内钙离子储备库的耗尽和药物抑制IP3信号转导抑制了轴突的伸展。微量注射竞争性IP3R阻滞剂肝素可引起轴突回缩。发色团辅助激光灭活导致生长锥中IP3R1功能的急性局部性丧失，导致生长锥停滞和突起回缩。IP3诱导的生长锥体内钙离子释放在神经生长控制中起着至关重要的作用，[Ca~(2+)]i的变化是调节卵子激活的重要因素。成熟的海鞘卵滞留在中期I，受精后观察到两个系列的[Ca~(2+)]_i瞬变：刚受精的Ca~(2+)波(系列I)和第一和第二极体排泄之间的[Ca~(2+)]_i振荡(系列II)。我们研究了果蝇卵子激活过程中胞内钙离子浓度升高的机制以及胞内钙离子瞬变的作用。抗IP3受体1型的单抗18A10可抑制IP3诱导的仓鼠和小鼠卵内钙离子释放，但对第I系和卵子变形无明显抑制作用，而对第II系和第一次细胞分裂有抑制作用。Ru红是Ryanodine受体介导的Ca~(2+)释放的抑制剂，对[Ca~(2+)]i瞬变和其他与卵子激活有关的事件没有明显的影响。

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.