EXOCYTOTIC SIGNALING THROUGH SPERM RECEPTORS FOR EGGS

通过精子受体向卵子发出胞外信号

• 批准号: 6693077
• 负责人: DAVID Joel MILLER
• 金额: $ 14.17万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693077
• 关键词: CD38 molecule; G protein; Xenopus oocyte; acrosome; benzoates; biological signal transduction; chimeric proteins; cytoplasm; egg /ovum; enzyme activity; enzyme inhibitors; exocytosis; fertility immunology; fertilization; galactosyltransferases; gene mutation; genetically modified animals; laboratory mouse; neutralizing antibody; protein tyrosine kinase

Our long-range objective is to develop a clearer fundamental understanding of the molecular basis of fertilization so that the process can be controlled to either promote fertilization or block it. Much progress has been made to identify ZP3, the protein in the mammalian egg coat that binds sperm and stimulates the acrosome reaction, the release of the acrosomal vesicle that must occur for sperm to penetrate the egg coat. Despite this progress, the identity of the ZP3 receptor on sperm has been elusive. One strong candidate is beta1,4-galactosyltransferase, an enzyme first discovered in the Golgi apparatus of somatic cells but later found on the surface of sperm. Beta1,4-Galactosyltransferase binds ZP3 but not other egg coat proteins. In addition to its role in gamete adhesion, beta1,4- galactosyltransferase acts to trigger the acrosome reaction in sperm. The acrosome reaction can be stimulated with antibodies to beta1,4-galactosyltransferase that act as mimics of ZP3 to bind and crosslink beta1,4-galactosyltransferase. There is evidence that binding beta1,4-galactosyltransferase stimulates at least some of the same signaling systems inside sperm that ZP3 stimulates, leading to the proposal that beta1,4- galactosyltransferase may be the major ZP3 receptor signaling the acrosome reaction. Mice with a targeted deletion of the beta1,4-galactosyltransferase gene, although fertile, produce sperm with severely compromised ability to acrosome react and penetrate the egg coat. In this proposal, the signaling systems that are activated by beta1,4-galactosyltransferase will be studied. The goals are to determine if binding beta1,4-galactosyltransferase specifically can completely reproduce all of the identified signaling systems activated by ZP3 binding, to study beta1,4-galactosyltransferase mutants to identify structural features necessary for signaling, and to identify proteins that interact with the portion of beta1,4- galactosyltransferase found in the cytosol. These studies will clarify the role of a sperm receptor for the egg coat in the acrosome reaction, a necessary step in the process of fertilization.

项目成果

Complexin I is required for mammalian sperm acrosomal exocytosis.

• DOI: 10.1016/j.ydbio.2007.07.009
• 发表时间: 2007-09
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Longmei Zhao;H. Burkin;Xudong Shi;Lingjun Li;K. Reim;David J. Miller

A proteomic approach to identify phosphoproteins encoded by cDNA libraries.

一种鉴定 cDNA 文库编码的磷蛋白的蛋白质组学方法。

• DOI: 10.1016/j.ab.2004.03.033
• 发表时间: 2004
• 期刊: Analytical biochemistry.
• 作者: Shi,Xudong;BeltonJr,RobertJ;Burkin,HeatherR;Vieira,AnaP;Miller,DavidJ
• 通讯作者: Miller,DavidJ

Dynamin 2 associates with complexins and is found in the acrosomal region of mammalian sperm.

Dynamin 2 与复合蛋白相关，存在于哺乳动物精子的顶体区域。

• DOI: 10.1002/mrd.20660
• 发表时间: 2007
• 期刊: Molecular reproduction and development
• 影响因子: 2.5
• 作者: Zhao,Longmei;Shi,Xudong;Li,Lingjun;Miller,DavidJ
• 通讯作者: Miller,DavidJ

Gamete interaction: is it species-specific?

配子相互作用：是否具有物种特异性？

• DOI: 10.1002/mrd.20542
• 发表时间: 2006
• 期刊: Molecular reproduction and development
• 影响因子: 2.5
• 作者: Vieira,Ana;Miller,DavidJ
• 通讯作者: Miller,DavidJ

Porcine sperm zona binding ability as an indicator of fertility.

猪精子带结合能力作为生育能力的指标。

• DOI: 10.1016/j.anireprosci.2007.01.012
• 发表时间: 2008
• 期刊: Animal reproduction science
• 影响因子: 2.2
• 作者: Collins,ED;Flowers,WL;Shanks,RD;Miller,DJ
• 通讯作者: Miller,DJ