RIM-BP3 is a manchette-associated protein essential for spermiogenesis

RIM-BP3 is a manchette-associated protein essential for spermiogenesis
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RIM-BP3 是精子发生必需的 manchette 相关蛋白

DOI:
10.1242/dev.030858
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发表时间:
2009-02
期刊:
影响因子:
4.6
通讯作者:
Ahmed Mansouri
Ahmed Mansouri
中科院分区:
生物学2区
文献类型:
--
作者:
杜雅蕊;黄燕女;韩代书;胡业广;周静;鲍兰;秦维华;徐国良;Ahmed Mansouri

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在精子发生过程中,哺乳动物的圆形精子细胞转化为活动精子。对精子形态发生的机制知之甚少。我们已经表征了一种新的蛋白质,RIM-BP 3,在小鼠精子细胞发育中具有专门的功能。RIM-BP 3蛋白与曼切特相关,曼切特是一种短暂的微管结构,被认为对精子发生过程中的形态发生很重要。RIM-BP 3基因的靶向缺失导致由于异常精子头部的男性不育,其特征在于变形的核和分离的顶体。与其在形态发生中的作用相一致,RIM-BP 3蛋白与Hook 1(一种已知的精子头部形态发生所需的manchette结合蛋白)物理关联。有趣的是,RIM-BP 3不与在azh(异常精子头)突变小鼠中表征的截短的Hook 1蛋白相互作用。此外,RIM-BP 3和Hook 1突变小鼠表现出几种常见的异常,特别是在精子细胞内的异位定位,精子头部畸形的推测原因。这些观察结果表明,RIM-BP 3通过与Hook 1的相互作用在Manchette发育和功能中发挥重要作用。由于畸形精子细胞的发生是导致精子功能障碍的常见异常之一,因此RIM-BP 3的鉴定可能提供对人类男性不育症潜在原因的分子线索的了解。
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.
DOI: 10.1073/pnas.162027899
发表时间: 2002-07
影响因子: 11.1
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