FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice.
FAM209 associates with DPY19L2, and is required for sperm acrosome biogenesis and fertility in mice.
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DOI：
10.1242/jcs.259206
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发表时间：
2021-11-01
影响因子：
4
通讯作者：
Matzuk MM
中科院分区：
文献类型：
--
作者：
Castaneda JM;Shimada K;Satouh Y;Yu Z;Devlin DJ;Ikawa M;Matzuk MM
不孕症每年困扰着全球15%的夫妇，其中50%的病例是男性造成的。球形精子症是一种罕见的不育男性，其特征是顶体生物发生缺陷，导致产生圆头精子。在这里，我们报告，家庭与序列相似性209（Fam209）是必需的顶体生物发生在小鼠精子。FAM209是哺乳动物中保守的小跨膜蛋白。Fam209的缺失导致继发于精子发生过程中顶体生物发生异常的生育缺陷，使人联想到球形精子症。对FAM209蛋白质组的分析鉴定了DPY19L2，其人类直向同源物涉及大多数球形精子症病例。虽然人类和小鼠DPY19L2的突变已被证明会导致球形精子症，但迄今为止尚未鉴定出DPY19L2的体内相互作用伴侣。FAM209与DPY19L2共定位在内核膜上以维持发育中的顶体。在这里，我们确定FAM209作为DPY19L2的第一个相互作用的伴侣，和第二个蛋白质，是必需的顶体生物发生定位到内核膜。摘要：我们报道了一个保守的新基因Fam209，是小鼠精子发育所必需的。在Fam209缺失的情况下观察到的表型与一些不育男性中有缺陷的精子的表型相似。
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. Summary: We report that a conserved novel gene, Fam209, is essential for sperm development in the mouse. The phenotype seen in the absence of Fam209 mimics that of defective sperm in some infertile men.
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影响因子：
9
作者：
El Zowalaty AE;Baumann C;Li R;Chen W;De La Fuente R;Ye X
通讯作者：
Ye X
影响因子：
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de Mateo, Sara;Castillo, Judit;Oliva, Rafael
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Oliva, Rafael
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Viville, Stephane
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Ray, Pierre F.
影响因子：
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通讯作者：
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