PDF(Pubmed)
Abstract：
Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.
摘要：
精子头部不仅包含细胞核，还包含顶体，顶体是位于细胞核前面的独特的帽状结构，源自高尔基体。高尔基体相关RAB2互分子（GARINs；也称为FAM71）蛋白家族在睾丸中显示出主要表达，并且都具有RAB2结合结构域，该结构域赋予与RAB2的结合亲和力，RAB2是一种小的GTP酶，负责膜运输和囊泡运输。我们先前的研究表明，GARIN1A和GARIN1B对于顶体生物发生很重要，而GARIN1B对于小鼠的雄性生育力是必不可少的。这里,我们产生了其他Garins的KO小鼠，即Garin2，Garin3，Garin4，Garin5a，和Garin5b（Garin2-5b）。使用计算机辅助形态分析，我们发现每个Garin2-5b的丢失导致精子头部形态发生异常。虽然Garin2-/-和Garin4-/-男性的受精是正常的，Garin5a-/-和Garin5b-/-雄性不育症，加林3-/-男性不育。进一步分析显示，Garin3-/-雄性表现出异常的顶体形态，但没有Garin1b-/-男性那么严重；相反，膜蛋白的数量，特别是ADAM家族蛋白，在Garin3KO精子中减少。此外，只有Garin4KO小鼠的精子头部出现空泡。这些结果表明，GARIN确保正确的头部形态发生，并且GARIN家族的某些成员在男性生育力中起着独特的作用。
