1月14日,《发育》 (Development) 杂志发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所研究人员关于RIM-BP3 (RIM-binding protein) 在精子形成方面的研究进展,揭示了RIM-BP3参与精子头部形态发生的机制,为男性不育的诊疗和计划生育药品的开发提供了潜在的药物靶点。该工作是在生化与细胞所徐国良研究员指导下完成的,博士研究生周静和杜雅蕊共同承担了主要的研究工作。同时生化与细胞所的鲍岚研究员、北京协和医科大学的韩代书教授以及德国马普生物物理化学研究所的Ahmed Mansouri教授也参与了合作。
目前,全球大约有15%的夫妇受到不育症的困扰,生殖健康逐渐引起了人们的普遍重视。为了从根本上实现对雄性不育的诊疗,需要对精子的发生过程和机制有更深入地了解。
本项工作中,研究人员将遗传学手段与形态学、分子生物学的方法结合起来,研究了RIM-BP3在精子形成 (spermiogenesis) 过程中的作用。他们的研究表明,RIM-BP3是一个在睾丸中特异表达的蛋白,主要在单倍体时期表达,胞内定位于精子领 (manchette) 上。小鼠中RIM-BP3基因的缺失会引起精子头部发育的异常,最终导致雄性不育。进一步的探索发现,RIM-BP3 与另一精子领结合蛋白Hook1在精子细胞内形成复合物,二者的相互作用在精子领的发育和功能方面发挥了不可或缺的作用。RIM-BP3在人和小鼠中高度同源,因此该基因可能在治疗男性不育和开发避孕药物方面有着潜在的应用价值。(生物谷Bioon.com)
生物谷推荐原始出处:
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.