Aster less Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila
Aster less Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila
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DOI：
10.1016/j.cub.2015.09.045
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发表时间：
2015-11-16
期刊：
影响因子：
9.2
通讯作者：
Avidor-Reiss, Tomer
中科院分区：
文献类型：
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作者：
Khire, Atul;Vizuet, Alberto A.;Avidor-Reiss, Tomer
中心体减少是精子细胞分化（精子发生）过程中中心体成分的减少[1，2]。它是导致精子形成的几种戏剧性的亚细胞重组之一，在许多动物中很常见[3]。然而，中心体减少的机制尚不清楚，其功能也不清楚。在这里，我们表明，在果蝇精子发生中，中心体蛋白的数量显着减少[4，5];例如，少紫菀（Asl）减少了500倍左右，在精子中几乎检测不到。Asl还原通过其结构域的子集由中心粒复制Plk 4的主调节因子[6-8]和靶向Plk 4进行降解的泛素连接酶：Slimb [9，10]调节。当Asl减少被Asl过表达、plk 4突变、Plk 4 RNAi或Slimb过表达减弱时，精子中的Asl水平更高，导致胚胎活力降低。值得注意的是，同时过表达Plk 4和Asl，或组合Plk 4和slimb突变，平衡了它们对Asl减少的相反作用，恢复了看似正常的生育力。这表明Asl水平升高导致观察到的生育力降低，而不是其他多效性效应。Asl减少的减弱也导致发育延迟和受精卵中星形微管形成的失败。总之，我们提供了第一个深入了解的分子机制，调节中心体减少和第一个直接的证据表明，中心体减少是受精后发育必不可少的。
Centrosonne reduction is the decrease in centrosomal components during spermatid differentiation (spermiogenesis) [1, 2]. It is one of several dramatic subcellular reorganizations that lead to spermatozoa formation common to a wide range of animals [3]. However, the mechanism underlying centrosome reduction is unknown and its functions are unclear. Here, we show that in Drosophila melanogaster spermiogenesis, the quantity of centrosomal proteins is dramatically reduced [4, 5]; for example, Aster less (Asl) is reduced similar to 500-fold and is barely detected in spermatozoa. Asl reduction is regulated through a subset of its domains by the master regulator of centriole duplication Plk4 [6-8] and by the ubiquitin ligase that targets Plk4 for degradation: Slimb [9, 10]. When Asl reduction is attenuated by Asl overexpression, plk4 mutations, Plk4 RNAi, or Slimb overexpression, Asl levels are higher in spermatozoa, resulting in embryos with reduced viability. Significantly, overexpressing Plk4 and Asl simultaneously, or combining plk4 and slimb mutations, balances their opposing effects on Asl reduction, restoring seemingly normal fertility. This suggests that increased Asl levels cause the observed reduced fertility and not other pleotropic effects. Attenuation of Asl reduction also causes delayed development and a failure to form astral microtubules in the zygote. Together, we provide the first insight into a molecular mechanism that regulates centrosome reduction and the first direct evidence that centrosome reduction is essential for post-fertilization development.