Infertility afflicts up to 15% of couples globally each year with men a contributing factor in 50% of these cases. Globozoospermia is a rare condition found in infertile men, which is characterized by defective acrosome biogenesis leading to the production of round-headed sperm. Here, we report that family with sequence similarity 209 (Fam209) is required for acrosome biogenesis in mouse sperm. FAM209 is a small transmembrane protein conserved among mammals. Loss of Fam209 results in fertility defects that are secondary to abnormalities in acrosome biogenesis during spermiogenesis, reminiscent of globozoospermia. Analysis of the FAM209 proteome identified DPY19L2, whose human orthologue is involved in the majority of globozoospermia cases. Although mutations in human and mouse Dpy19l2 have been shown to cause globozoospermia, no in vivo interacting partners of DPY19L2 have been identified until now. FAM209 colocalizes with DPY19L2 at the inner nuclear membrane to maintain the developing acrosome. Here, we identified FAM209 as the first interacting partner of DPY19L2, and the second protein that is essential for acrosome biogenesis that localizes to the inner nuclear membrane.

中文翻译：

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FAM209 与 DPY19L2 结合，是小鼠精子顶体生物发生和生育所必需的。

全球每年有多达 15% 的夫妇患有不孕症，其中 50% 的病例是男性。Globozoospermia 是在不育男性中发现的一种罕见疾病，其特征是有缺陷的顶体生物发生，导致产生圆头精子。在这里，我们报告了具有序列相似性 209 (Fam209) 的家族是小鼠精子顶体生物发生所必需的。FAM209 是一种在哺乳动物中保守的小跨膜蛋白。Fam209 的缺失导致生育缺陷，继发于精子发生过程中顶体生物发生异常，让人联想到球形精子症。对 FAM209 蛋白质组的分析确定了 DPY19L2，其人类直系同源物与大多数球形精子症病例有关。虽然人类和小鼠 Dpy19l2 的突变已被证明会导致球形精子症，到目前为止，还没有发现 DPY19L2 的体内相互作用伙伴。FAM209 与 DPY19L2 共定位在内核膜以维持正在发育的顶体。在这里，我们将 FAM209 确定为 DPY19L2 的第一个相互作用伙伴，以及定位于内核膜的顶体生物发生所必需的第二种蛋白质。