Molecular and functional characterization of the novel role of HERC4 in spermiogenesis.

我们研究的长期目标是提高我们对人类HERC蛋白新家族生物学功能的认识。herc具有两个独特的结构特征，称为RLD和HECT结构域，被认为是从动物进化早期不同基因之间的融合事件进化而来的。进化上不同物种的HERC蛋白具有非常高的同源性，这意味着该蛋白家族的功能在整个动物界都是保守的。我们的短期目标是开发一种可用于评估所有人类HERC蛋白功能的模型系统。我们目前的重点是HERC4，因为它是herc家族中最古老的基因，所有其他herc成员都是从herc家族中衍生出来的。人类HERC4的生物学作用尚不清楚；然而，小鼠HERC4是小鼠精子正常成熟所必需的，并且与小鼠雄性不育有关。我们的研究将推进对HERC4生物学功能的基本认识，它可能被证明是生物学中最基本的细胞过程之一——精子发育的关键因素。我们的研究将深入了解为什么HERC4是精子正常发育所必需的，以及为什么HERC4缺陷与小鼠雄性不育有关。

The long-term goal of our research is to advance our knowledge of the biological functions of the novel family of human HERC proteins. HERCs possess two unique structural features called an RLD and a HECT domain that are thought to have evolved from a fusion event between different genes very early in animal evolution. There is a remarkably high degree of homology among HERC proteins from evolutionarily diverse species, implying that the functions of this family of proteins are conserved throughout the animal kingdom. Our short-term goal is to develop a model system that can be used to evaluate the functions of all human HERC proteins. Our current focus is on HERC4 since it is the oldest gene of the herc family, from which all other herc members were derived. The biological role of human HERC4 is unknown; however murine HERC4 is required for proper maturation of sperm in mice and is associated with male infertility in mice. Our research will advance basic knowledge of the biological function of HERC4, which may prove to be a critical factor in one of the most fundamental cellular processes in biology, the development of sperm. Our research will provide insight into why HERC4 is required for the proper development of sperm and why defective HERC4 is associated with male infertility in mice.