Golga3的蛋白功能及与Golga3(repro27)雄鼠不育分子机制的研究

The Golga3(repro27) mutant males exhibit defects in germ cell development that culminate in testicular atrophy, low epididymal sperm concentration, low motility, and unsuccessful in vitro fertilization. Although preliminary studies have indicated that Golga3 protein plays an important role in apoptotic signaling and Golgi complex mediated protein targeting in testis, the detailed molecular mechanism of infertility is still unknown. Mouse Golga3 shows conserved amino acid structures with human GOLGA3, which interacts with GOPC （Golgi-associated PDZ-and coiled-coil motif-containing protein）. In our study, we will utilize yeast two-hybrid experiments to identify interacting proteins of Golga3 and also identify differentiated expressed proteins based on quantitative proteomic analysis. By further analysis of the interacting proteins and constructing functional networks of differentiated expressed proteins, we could further find the detailed molecular mechanisms of male infertility. In this study, we will explore the functions of Golga3 to facilitate mechanism studies of male infertility, which will provide new clues for diagnosis and treatment of male infertility.

Golga3(repro27)突变鼠表现出生殖细胞缺陷进而导致睾丸萎缩，其附睾产生的精子浓度和活动性下降,且这些精子会导致体外受精失败。初步研究表明Golga3在睾丸中的细胞凋亡信号通路和高尔基体复合物动态变化中起到作用，但是Golga3基因突变导致不育的具体分子机制还需进一步的探讨。老鼠与人的GOLGA3氨基酸序列结构相似，可推测与含有PDZ和卷曲螺旋基序的与高尔基体相关的蛋白（GOPC）相互作用。在本研究中，我们拟利用酵母菌双杂交实验方法鉴别出在睾丸中与Golga3相互作用的蛋白，并且利用蛋白组学分析鉴别出突变老鼠和对照鼠中有表达量差异的蛋白。通过分析这些相互作用的蛋白质的功能和对不同表达量的蛋白构建功能网络，探究导致雄鼠不育的具体分子机制。本研究以发掘Golga3的蛋白功能为新视点，为探究Golga3突变导致雄鼠不育的发生机制奠定基础，为男性不育的诊断和治疗提供新的思路。