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Molecular bases that ensure genomic inheritance through successive generations

确保基因组遗传代代相传的分子基础

基本信息

批准号：
17207011
负责人：
KISHIMOTO Takeo
金额：
$ 31.45万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Based on the cell cycle control and the nuclear formation, molecular mechanisms that ensure genomic inheritance through successive generations have been studied in oocytes and eggs of starfish and frog.1. Meiotic reinitiation : We had previously showed that the signaling pathway that leads to meiotic reinitiation in starfish oocytes is composed of the putative receptor for maturation-inducing hormone, 1-MeAde/hetero-trimeric G-protein/PI3-kinase/Akt/cyclin B-Cdc2/Plk1. Here, we tried to isolate the 1-MeAde receptor using affinity ferrite beads. Three peptides of 42, 92 and 97 kDa which should possibly consitute the receptor were identified. In addition, we found that activation of Aurora, a mitotic kinase, completely depends on activation of cyclin B-Cdc2 at meiotic reinitiation in starfish oocytes ; and that a single type of starfish Aurora exhibits both functions of Aurora A and B, each of which has distinct functions in HeLa cells.2. Meiotic metaphase-II arrest and its release : In Xenopus oocytes, we demonstrated that meta-II arrest is induced by direct phosphorylation of Erp1 with p9ORsk, which enhances both stability of Erp1 and its inhibitory activity against APC/C, thereby preventing the APC/C-mediated degradation of cyclin B.At release from meta-II arrest, we showed that in addition to previously known CaMKII, transient activation of calcineurin is required for Erp1 degradation and restart of the cell cycle.3. Formation of male and female pronuclei : In immature Xenopus oocytes, we found that importin α-mediated nuclear transport is suppressed due to its trapping into annulate lamellae, and that the trapping is cancelled at meiotic reinitiation. This should contribute to acqusition of the pronuclear formation ability during meiotic maturation. Further, we showed in starfish eggs that pronuclear congression and fusion after fertilization do not depend on the cell cycle progression.

基于细胞周期控制和细胞核形成，研究了海星和青蛙卵母细胞基因组遗传的分子机制。减数分裂再起始：我们之前已经表明，导致海星卵母细胞减数分裂再起始的信号通路是由成熟诱导激素的公认受体，1-MeAde/异三聚体g蛋白/ pi3激酶/Akt/cyclin B-Cdc2/Plk1组成的。在这里，我们试图用亲和铁氧体珠分离1-MeAde受体。鉴定了可能构成受体的3个肽段，分别为42、92和97 kDa。此外，我们发现有丝分裂激酶Aurora的激活完全依赖于海星卵母细胞减数分裂再起始时细胞周期蛋白B-Cdc2的激活；一种类型的极光海星同时具有极光a和极光B的功能，它们在海拉细胞中具有不同的功能。减数分裂中期ii阻滞及其释放：在非洲爪蟾卵母细胞中，我们证明了meta-II阻滞是由p9ORsk直接磷酸化Erp1诱导的，这增强了Erp1的稳定性及其对APC/C的抑制活性，从而阻止了APC/C介导的细胞周期蛋白b的降解。在meta-II阻滞的释放中，我们发现除了先前已知的CaMKII外，Erp1降解和细胞周期重启还需要钙调磷酸酶的短暂激活。雄性和雌性原核的形成：在未成熟的爪蟾卵母细胞中，我们发现输入α-介导的核运输由于其被捕获到环状片而受到抑制，并且在减数分裂再起始时被取消捕获。这应该有助于在减数分裂成熟过程中获得原核形成能力。此外，我们在海星卵中发现，受精后的原核形成和融合不依赖于细胞周期的进展。