Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054, USA.
Development. 2011 Mar;138(6):1111-20. doi: 10.1242/dev.057422.
Clathrin has previously been implicated in Drosophila male fertility and spermatid individualization. To understand further the role of membrane transport in this process, we analyzed the phenotypes of mutations in Drosophila auxilin (aux), a regulator of clathrin function, in spermatogenesis. Like partial loss-of-function Clathrin heavy chain (Chc) mutants, aux mutant males are sterile and produce no mature sperm. The reproductive defects of aux males were rescued by male germ cell-specific expression of aux, indicating that auxilin function is required autonomously in the germ cells. Furthermore, this rescue depends on both the clathrin-binding and J domains, suggesting that the ability of Aux to bind clathrin and the Hsc70 ATPase is essential for sperm formation. aux mutant spermatids show a deficit in formation of the plasma membrane during elongation, which probably disrupts the subsequent coordinated migration of investment cones during individualization. In wild-type germ cells, GFP-tagged clathrin localized to clusters of vesicular structures near the Golgi. These structures also contained the Golgi-associated clathrin adaptor AP-1, suggesting that they were Golgi-derived. By contrast, in aux mutant cells, clathrin localized to abnormal patches surrounding the Golgi and its colocalization with AP-1 was disrupted. Based on these results, we propose that Golgi-derived clathrin-positive vesicles are normally required for sustaining the plasma membrane increase necessary for spermatid differentiation. Our data suggest that Aux participates in forming these Golgi-derived clathrin-positive vesicles and that Aux, therefore, has a role in the secretory pathway.
网格蛋白先前被牵涉到果蝇雄性的生育能力和精细胞的个体化。为了进一步了解在这个过程中膜运输的作用,我们分析了果蝇辅助蛋白(aux)突变在精子发生中的表型,aux 是网格蛋白功能的调节剂。像部分功能丧失的网格蛋白重链(Chc)突变体一样,aux 突变体雄性是不育的,不能产生成熟的精子。aux 雄性的生殖缺陷可以通过雄性生殖细胞特异性表达 aux 来挽救,这表明 auxilin 功能在生殖细胞中是自主需要的。此外,这种挽救依赖于网格蛋白结合和 J 结构域,这表明 Aux 结合网格蛋白和 Hsc70 ATP 酶的能力对于精子形成是必不可少的。aux 突变体精细胞在伸长过程中表现出质膜形成不足,这可能破坏随后个体化过程中投资锥体的协调迁移。在野生型生殖细胞中,GFP 标记的网格蛋白定位于高尔基体附近的囊泡结构簇中。这些结构还包含与高尔基体相关的网格蛋白衔接蛋白 AP-1,这表明它们是高尔基体衍生的。相比之下,在 aux 突变细胞中,网格蛋白定位于高尔基体周围的异常斑块,其与 AP-1 的共定位被破坏。基于这些结果,我们提出高尔基体衍生的网格蛋白阳性囊泡通常是维持精细胞分化所需的质膜增加所必需的。我们的数据表明,Aux 参与形成这些高尔基体衍生的网格蛋白阳性囊泡,因此,Aux 在分泌途径中具有作用。