Novel CatSper3 and CatSper4 Ion Channel Genes in Sperm

精子中的新型 CatSper3 和 CatSper4 离子通道基因

• 批准号: 6703190
• 负责人: DAVID E. CLAPHAM
• 金额: $ 32.81万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6703190
• 关键词: biological signal transduction; calcium channel; cell differentiation; cell line; fertility; fluorescent dye /probe; genetically modified animals; laboratory mouse; molecular biology; phenotype; protein protein interaction; protein structure function; reproductive development; sperm; sperm motility; voltage gated channel; yeast two hybrid system

DESCRIPTION (provided by applicant): The fusion of sperm and egg lead to the combination of the father's and mother's genetic information to create a new individual. In humans, as in all mammals, sperm must reach the egg, penetrate its protective coat, fuse with the oocyte membrane, and deliver its genetic material. Ion channels in the sperm mediate many of these steps. We have identified four ion channels that are in sperm but not other tissues. CatSpers (Cation channel of Sperm) are six transmembrane-spanning ion channel proteins localized primarily to the tail of mature sperm (Ren et al, 2001). CatSper1 is an ion channel that triggers calcium-influx into the principal piece of the sperm tail. Male mice homozygous for null-mutations in the CatSper1 gene are 100% infertile, but otherwise are completely normal. Sperm from mice genetically engineered to lack the functional CatSper1 gene show a significant reduction in motility and are incapable of penetrating through the outer coat of an egg. We have identified two new sperm-specific proteins, CatSper3 and CatSper4 that are localized to the sperm tail. Experiments are proposed that will delineate the function of these novel ion channels and reveal their role in sperm function. Understanding these proteins will increase our understanding of fertilization and shed light on both some causes of male infertility as well as provide new targets for contraceptive agents.

描述（由申请人提供）：精子和卵子的融合导致父亲和母亲的遗传信息的结合，以创造一个新的个体。人类和所有哺乳动物一样，精子必须到达卵子，穿透其保护层，与卵母细胞膜融合，并传递其遗传物质。精子中的离子通道介导了许多这些步骤。我们已经确定了四种离子通道，它们存在于精子中，而不是其他组织。CatSpers（精子阳离子通道）是主要定位于成熟精子尾部的六种跨膜离子通道蛋白（Ren et al，2001）。CatSper1是一种离子通道，它触发钙流入精子尾部的主要部分。CatSper 1基因中的空突变纯合子雄性小鼠100%不育，但其他方面完全正常。来自基因工程小鼠的精子缺乏功能性CatSper 1基因，表现出运动性显著降低，并且无法穿透卵子的外层。 我们已经确定了两个新的精子特异性蛋白，CatSper3和CatSper4，定位于精子尾部。实验提出，将描绘这些新的离子通道的功能，并揭示其在精子功能中的作用。了解这些蛋白质将增加我们对受精的理解，揭示男性不育的一些原因，并为避孕药提供新的靶点。