FAM209 associates with DPY19L2 and is required for sperm acrosome biogenesis and fertility in mice.
2021
Infertility afflicts up to 15% of couples globally each year with men a contributing factor in half of these cases. Globozoospermia is a rare condition found in infertile men that is characterized by defective acrosome biogenesis leading to the production of round shaped sperm. Here, we report a novel gene, Fam209 (Family with sequence similarity 209), that is required for acrosome biogenesis in mouse sperm. FAM209 is a small transmembrane protein conserved among mammals. Loss of Fam209 result in fertility defects secondary to abnormalities in acrosome biogenesis during spermiogenesis reminiscent of globozoospermia. Proteomic analysis of the FAM209 proteome identified DPY19L2, a protein involved in the majority of globozoospermia cases. While 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 to the inner nuclear membrane to maintain the developing acrosome. This report identifies FAM209 as the first interacting partner of DPY19L2 and the second protein that is essential for acrosome biogenesis and that co-localizes with DPY19L2 to the inner nuclear membrane.
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