Lack of acrosome formation in mice lacking a Golgi protein, GOPC
Lack of acrosome formation in mice lacking a Golgi protein, GOPC
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DOI：
10.1073/pnas.162027899
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发表时间：
2002-07
影响因子：
11.1
通讯作者：
R. Yao;C. Ito;Yasuko Natsume;Yoshinobu Sugitani;H. Yamanaka;Shoji Kuretake;K. Yanagida;A. Sato;K. Toshimori;T. Noda
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文献类型：
--
作者：
R. Yao;C. Ito;Yasuko Natsume;Yoshinobu Sugitani;H. Yamanaka;Shoji Kuretake;K. Yanagida;A. Sato;K. Toshimori;T. Noda
顶体是一种独特的细胞器，在受精过程中精子与透明质酸结合的部位起重要作用，在人类遗传性不育综合征--球形精子症中丢失。虽然已知顶体来源于高尔基体，但顶体形成的分子机制在很大程度上是未知的。在这里，我们表明，高尔基体相关的PDZ和卷曲螺旋基序的蛋白质（GOPC），最近确定的高尔基体相关蛋白，主要是位于在圆形精子细胞的trans-Golgi区域，和雄性小鼠，其中GOPC已被破坏是不育的球形精子。早期圆形精子细胞的主要缺陷是顶体碎裂，出现了不能与发育中的顶体融合的异常小泡。在晚期，观察到核畸形和线粒体排列异常，这也是人类球形精子症的特征。有趣的是，将这种畸形精子注射到卵母细胞中的卵胞浆内单精子注射（ICSI）仅在注射的卵母细胞被激活时才导致卵裂成囊胚。因此，GOPC为了解精子发生机制提供了重要线索，GOPC缺陷小鼠可能是人类球形精子症的独特而有价值的模型。
The acrosome is a unique organelle that plays an important role at the site of sperm–zona pellucida binding during the fertilization process, and is lost in globozoospermia, an inherited infertility syndrome in humans. Although the acrosome is known to be derived from the Golgi apparatus, molecular mechanisms underlying acrosome formation are largely unknown. Here we show that Golgi-associated PDZ- and coiled-coil motif-containing protein (GOPC), a recently identified Golgi-associated protein, is predominantly localized at the trans-Golgi region in round spermatids, and male mice in which GOPC has been disrupted are infertile with globozoospermia. The primary defect was the fragmentation of acrosomes in early round spermatids, and abnormal vesicles that failed to fuse to developing acrosomes were apparent. In later stages, nuclear malformation and an abnormal arrangement of mitochondria, which are also characteristic features of human globozoospermia, were observed. Interestingly, intracytoplasmic sperm injection (ICSI) of such malformed sperm into oocytes resulted in cleavage into blastocysts only when injected oocytes were activated. Thus, GOPC provides important clues to understanding the mechanisms underlying spermatogenesis, and the GOPC-deficient mouse may be a unique and valuable model for human globozoospermia.