Khire Atul, Vizuet Alberto A, Davila Enrique, Avidor-Reiss Tomer
Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA.
Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA.
Curr Biol. 2015 Nov 16;25(22):2956-63. doi: 10.1016/j.cub.2015.09.045. Epub 2015 Oct 17.
Centrosome reduction is the decrease in centrosomal components during spermatid differentiation (spermiogenesis). It is one of several dramatic subcellular reorganizations that lead to spermatozoa formation common to a wide range of animals. 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; for example, Asterless (Asl) is reduced ∼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 and by the ubiquitin ligase that targets Plk4 for degradation: Slimb. 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.
中心体减少是指在精子细胞分化（精子发生）过程中中心体成分的减少。它是导致多种动物精子形成的几种显著的亚细胞重组之一。然而，中心体减少的潜在机制尚不清楚，其功能也不明确。在这里，我们表明，在黑腹果蝇精子发生过程中，中心体蛋白的数量显著减少；例如，无星状体（Asl）减少了约500倍，在精子中几乎检测不到。Asl的减少是由中心粒复制的主要调节因子Plk4及其靶向Plk4进行降解的泛素连接酶：Slimb通过其一部分结构域来调节的。当通过Asl过表达、plk4突变、Plk4 RNA干扰或Slimb过表达减弱Asl减少时，精子中的Asl水平会升高，导致胚胎活力降低。值得注意的是，同时过表达Plk4和Asl，或者将plk4和slimb突变结合起来，可以平衡它们对Asl减少的相反作用，恢复看似正常的生育能力。这表明Asl水平升高导致了观察到的生育能力下降，而不是其他多效性效应。Asl减少的减弱还会导致发育延迟以及合子中星体微管无法形成。总之，我们首次深入了解了调节中心体减少的分子机制，并且首次获得了直接证据，证明中心体减少对受精后发育至关重要。
