Globozoospermia and lack of acrosome formation in GM130-deficient mice.
Globozoospermia and lack of acrosome formation in GM130-deficient mice.
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GM130 缺陷小鼠的球精子症和顶体形成缺乏
DOI：
10.1038/cddis.2016.414
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发表时间：
2017-01-05
影响因子：
9
通讯作者：
Gao F
中科院分区：
文献类型：
--
作者：
Han F;Liu C;Zhang L;Chen M;Zhou Y;Qin Y;Wang Y;Chen M;Duo S;Cui X;Bao S;Gao F
球形精子症是一种常见的导致男性不育的生殖系统疾病，顶体畸形或缺失是其显著特征。虽然顶体被认为是来源于高尔基体，详细的分子机制仍不清楚。GM 130是一种位于高尔基体基质顺式侧的蛋白质，然而该蛋白质的生理功能仍然是难以捉摸的。在这里，我们表明，在小鼠模型中，GM 130的失活导致男性不育。主要缺陷是缺乏顶体，圆形精子头，线粒体鞘的异常组装，这包括人类球形精子症的特征。进一步的研究表明，GM 130的损失并不影响前顶体囊泡的分泌，而囊泡未能融合成一个单一的大顶体囊泡。共定位的衔接蛋白复合物AP 1和trans-Golgi网络（TGN）蛋白TGN 46被破坏，这表明顶体的畸形是最有可能由于在高尔基体衍生的前顶体囊泡的分选和涂层的缺陷。因此，GM 130缺陷小鼠为研究人类球形精子症的病因提供了一个有价值的模型。
Globozoospermia is a common reproductive disorder that causes male infertility in humans, and the malformation or loss of acrosomes is the prominent feature of this disease. Although the acrosome is thought to be derived from the Golgi apparatus, the detailed molecular mechanisms remain unclear. GM130 is a cis-side localized Golgi matrix protein,whereas the physiological functions of this protein remain elusive. Here we showed that inactivation of GM130-caused male infertility in mouse model. The primary defects were the absence of acrosomes, round sperm heads, and aberrant assembly of the mitochondrial sheath, which comprise the characteristic features of human globozoospermia. Further investigation indicated that loss of GM130 did not affect the secretion of pro-acrosomic vesicles, whereas the vesicles failed to fuse into a single large acrosome vesicle. Co-localization of the adaptor protein complex AP1 and trans-Golgi network (TGN) protein TGN46 was disrupted, suggesting that the malformation of acrosomes is most likely due to the defect in the sorting and coating of Golgi-derived pro-acrosomic vesicles. Thus, the GM130-deficient mouse provides a valuable model for investigating the etiology of human globozoospermia.