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Signal transduction pathways leading to Ca2+ release in fertilization: focusing on egg membrane-associated protein complexes

导致受精过程中 Ca2 释放的信号转导途径：关注卵膜相关蛋白复合物

基本信息

批准号：
16570174
负责人：
SATO Ken-ichi
金额：
$ 2.3万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16570174/
关键词：
fertilization signal transduction membrane rafts Src egg activation uroplakin III gamete interaction early development

项目摘要

We have analyzed molecular mechanism of fertilization by using African clawed frog Xenopus laevis as a main model organism. By focusing on molecular identity of a 57-kDa protein-tyrosine kinase that is immunochemically related to the Src family kinases and the structure and function of the egg plasma membrane-associated protein complexes, we have found that Xenopus Src gene product (termed xSrc) and a 30-kDa transmembrane protein uroplakin III (termed xUPIII) are important factors for sperm-induced egg activation, namely transient Ca2+ release within the fertilized egg. xUPIII has been initially identified as a major tyrosine-phosphorylated protein in fertilized Xenopus eggs. Further analysis of xUPIII has demonstrated that it is a target of sperm-derived protease activity and that partial proteolysis of the extracellular domain of xUPIII at fertilization may act as a signal to promote sperm-induced xSrc activation. Because both xUPIII and Src localizes predominantly in cholesterol-enriched egg membrane microdomains or "rafts", it is assumed that protein complexes organized in the membrane microdomains serve as a functional platform for sperm-egg membrane interaction and subsequent Src-dependent calcium signaling at fertilization. We have also identified uroplakin Ib (termed xUPIb), as a binding partner for UPIII and expression studies using HEK293 cells show that co-expression of xUPIII and xUPIb is required for their proper localization to the membrane microdomain as well as maintenance of xSrc tyrosine kinase activity in an inactive state. These results highlights the scheme that sperm-induced egg activation in Xenopus involves molecular machinery that act for gamete interaction in the extracellular space and that translates the sperm signal into the intracellular space, both of which are localized in the egg membrane microdomains

以非洲爪蟾为主要模式生物，分析了非洲爪蟾受精的分子机制。通过关注与Src家族激酶免疫化学相关的57-kDa蛋白酪氨酸激酶的分子特性以及卵质膜相关蛋白复合物的结构和功能，我们发现非洲爪蟾Src基因产物（称为xSrc）和30-kDa跨膜蛋白uroplakin III（称为xUPIII）是精子诱导的卵子激活的重要因素，即受精卵内的瞬时Ca 2+释放。xUPIII最初被鉴定为非洲爪蟾受精卵中的主要酪氨酸磷酸化蛋白。xUPIII的进一步分析表明，它是精子衍生的蛋白酶活性的目标，并且在受精时xUPIII的胞外结构域的部分蛋白水解可以作为促进精子诱导的xSrc激活的信号。由于xUPIII和Src主要定位于富含胆固醇的卵膜微区或“筏”中，因此假定在膜微区中组织的蛋白质复合物充当精卵膜相互作用和随后的受精时Src依赖性钙信号传导的功能平台。我们还确定了尿斑蛋白Ib（称为xUPIb）作为UPIII的结合伴侣，使用HEK 293细胞的表达研究表明，xUPIII和xUPIb的共表达是其正确定位于膜微区以及维持xSrc酪氨酸激酶活性处于非活性状态所必需的。这些结果强调了非洲爪蟾精子诱导的卵子激活涉及细胞外空间中配子相互作用和将精子信号翻译到细胞内空间的分子机制，这两者都位于卵膜微区

项目成果

期刊论文数量（76）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Egg fertilizome : From transmembrane signaling to translational control of gene expression in the initiation of development : Focus on Genome Research(Williams, C.R.ed.)

卵子受精组：从跨膜信号转导到发育起始中基因表达的翻译控制：关注基因组研究（Williams，C.R.ed.）

DOI：
发表时间：
2004
期刊：
影响因子：
0
作者：
Takaku;Y.;Sato et al.;Daniel A.Peiffer et al.;Sato K.et al.
通讯作者：
Sato K.et al.

Molecular dissection of egg fertilization signaling with the aid of tyrosine kinase-specific inhibitor and activator strategies

DOI：
10.1016/j.bbapap.2003.11.017
发表时间：
2004-03-11
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
影响因子：
3.2
作者：
Sato, K;Iwasaki, T;Fukami, Y
通讯作者：
Fukami, Y

Fertilizome project : Study on the biological bridge between ametogenesis and embryogenesis

Fertilizome项目：无细胞发育和胚胎发生之间的生物桥研究

DOI：
发表时间：
2004
期刊：
Current Proteomics 1
影响因子：
0
作者：
Sakakibara;K.;Sato.K.;Yoshino;K.;Oshiro;N.;Hirahara;S.;Hasan;A.K.M.M.;Iwasaki;T.;Ueda;Y.;Iwao;Y.;Yonezawa;K.;Fukami;Y.;Tokmakov et al.;Sato K.et al.;Sato K.et al.;Sakakibara K. et al.;Sato et al.;Kurokawa et al.;Sato et al.
通讯作者：
Sato et al.

Phylogeny of vertebrate Src tyrosine kinase as revealed by the epitope region for mAb327.

mAb327 的表位区域揭示了脊椎动物 Src 酪氨酸激酶的系统发育。