1月14日,，《發(fā)育》 (Development) 雜志發(fā)表了中國科學院上海生命科學研究院生物化學與細胞生物學研究所研究人員關于RIM-BP3 (RIM-binding protein) 在精子形成方面的研究進展,，揭示了RIM-BP3參與精子頭部形態(tài)發(fā)生的機制，為男性不育的診療和計劃生育藥品的開發(fā)提供了潛在的藥物靶點,。該工作是在生化與細胞所徐國良研究員指導下完成的,，博士研究生周靜和杜雅蕊共同承擔了主要的研究工作。同時生化與細胞所的鮑嵐研究員、北京協(xié)和醫(yī)科大學的韓代書教授以及德國馬普生物物理化學研究所的Ahmed Mansouri教授也參與了合作,。
目前,，全球大約有15％的夫婦受到不育癥的困擾，生殖健康逐漸引起了人們的普遍重視,。為了從根本上實現對雄性不育的診療,，需要對精子的發(fā)生過程和機制有更深入地了解。
本項工作中,，研究人員將遺傳學手段與形態(tài)學,、分子生物學的方法結合起來，研究了RIM-BP3在精子形成 (spermiogenesis) 過程中的作用,。他們的研究表明,，RIM-BP3是一個在睪丸中特異表達的蛋白，主要在單倍體時期表達,，胞內定位于精子領 (manchette) 上,。小鼠中RIM-BP3基因的缺失會引起精子頭部發(fā)育的異常，最終導致雄性不育,。進一步的探索發(fā)現,，RIM-BP3 與另一精子領結合蛋白Hook1在精子細胞內形成復合物，二者的相互作用在精子領的發(fā)育和功能方面發(fā)揮了不可或缺的作用,。RIM-BP3在人和小鼠中高度同源,，因此該基因可能在治療男性不育和開發(fā)避孕藥物方面有著潛在的應用價值。（生物谷Bioon.com）
生物谷推薦原始出處：
Development 136, 373-382 (2009) doi: 10.1242/dev.030858
RIM-BP3 is a manchette-associated protein essential for spermiogenesis
Jing Zhou1,*, Ya-Rui Du1,*, Wei-Hua Qin1,, Ye-Guang Hu1, Yan-Nv Huang1, Lan Bao2, Daishu Han3, Ahmed Mansouri4 and Guo-Liang Xu1,
1 The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
2 The Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
3 Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China.
4 Max Planck Institute of Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Goettingen, Germany.
During spermiogenesis, round spermatids are converted into motile sperm in mammals. The mechanisms responsible for sperm morphogenesis are poorly understood. We have characterized a novel protein, RIM-BP3, with a specialized function in spermatid development in mice. The RIM-BP3 protein is associated with the manchette, a transient microtubular structure believed to be important for morphogenesis during spermiogenesis. Targeted deletion of the RIM-BP3 gene resulted in male infertility owing to abnormal sperm heads, which are characterized by a deformed nucleus and a detached acrosome. Consistent with its role in morphogenesis, the RIM-BP3 protein physically associates with Hook1, a known manchette-bound protein required for sperm head morphogenesis. Interestingly, RIM-BP3 does not interact with the truncated Hook1 protein characterized in azh (abnormal spermatozoon head) mutant mice. Moreover, RIM-BP3 and Hook1 mutant mice display several common abnormalities, in particular with regard to the ectopic positioning of the manchette within the spermatid, a presumed cause of sperm head deformities. These observations suggest an essential role for RIM-BP3 in manchette development and function through its interaction with Hook1. As the occurrence of deformed spermatids is one of the common abnormalities leading to malfunctional sperm, identification of RIM-BP3 might provide insight into the molecular cue underlying causes of male infertility in humans.
