精子的鞭毛发育与运动是精子行使运动功能的最重要的发育过程。在这一过程中精子中心粒的生成与转运是精子鞭毛形成的重要环节。在精子尾部发育的关键蛋白均与这个结构有关系，然而在这个转运过程中的分子机制仍然并不清楚。我们在前期的研究中利用在近亲结婚的短尾精子家系通过外显子组测序发现一个控制精子鞭毛发育的关键蛋白QRICH2, 蛋白组学结果提示其控制鞭毛发育过程中的结构与能量代谢的关键蛋白。但是其调控这两类蛋白的具体机制尚待深入研究。本研究将着重研究：1）QRICH2在外源的pH,Ca2+等离子梯度调节下，如何在精子尾部鞭毛形成过程中，转运到精子尾部的中心体？2）QRICH2的不同结构域如何负责精子尾部鞭毛结构与能量代谢这两类蛋白的转运与代谢? 3) Qrich2突变小鼠的ICSI结局如何。我们的研究将可能揭示QRICH2在精子鞭毛发育早期中心粒形成及以中心粒为核心的鞭毛发育中的作用。

The development and movement of sperm flagella is the most important developmental process for sperm to gain the motor function. In this process, the formation and transport of sperm centrosome is an important milestone in the forming of sperm flagella. The key proteins expressed at the tail of the sperm are related to this structure, but the key molecular mechanisms in this transport process are still unclear. In the previous study, we used exome sequencing and have identified a candiadate gene,QRICH2, in consanguious pedgrees with short sperm tail, and experiments show it play critical role in sperm flagella development. Proteomics results suggested that it controls the expression of two types of proteins including structure and energy metabolism during the development of flagella. But its specific mechanism for regulating these proteins is not clear. This study will focus on: 1) Under the external enviroment of pH,Ca2+ ion gradient, how the expression and transportation of QRICH2 is regulated to be involved in flagella formation; 2) How the different domains of QRICH2 are responsible for the transport and metabolism of two types of proteins, including the structure proteins and proteins related to energy metabolism? 3) What's the health status of the ICSI offspring for Qrich2 mutant mice. Our research will probably reveal the role of QRICH2 in the development of sperm centrosme and flagella and provide a key mechanistic insight of flagella development.