Department of Biology, Yeshiva University, New York, NY 10033, USA
Department of Biology, Yeshiva University, New York, NY 10033, USA.
Development. 2019 Sep 2;146(17):dev179275. doi: 10.1242/dev.179275.
Gamete formation is key to survival of higher organisms. In male animals, spermatogenesis gives rise to interconnected spermatids that differentiate and individualize into mature sperm, each tightly enclosed by a plasma membrane. In , individualization of sister spermatids requires the formation of specialized actin cones that synchronously move along the sperm tails, removing inter-spermatid bridges and most of the cytoplasm. Here, we show that Combover (Cmb), originally identified as an effector of planar cell polarity (PCP) under control of Rho kinase, is essential for sperm individualization. mutants are male sterile, with actin cones that fail to move in a synchronized manner along the flagella, despite being correctly formed and polarized initially. These defects are germline autonomous, independent of PCP genes, and can be rescued by wild-type Cmb, but not by a version of Cmb in which known Rho kinase phosphorylation sites are mutated. Furthermore, Cmb binds to the axonemal component Radial spoke protein 3, knockdown of which causes similar individualization defects, suggesting that Cmb coordinates the individualization machinery with the microtubular axonemes.
配子形成是高等生物生存的关键。在雄性动物中，精子发生导致相互连接的精母细胞分化并个体化成为成熟精子，每个精子都被质膜紧密包裹。在这里，我们表明，最初被鉴定为 Rho 激酶控制的平面细胞极性 (PCP) 效应物的 Combover (Cmb) 对于精子个体化是必不可少的。Cmb 突变体是雄性不育的，其有丝分裂锥不能沿着鞭毛以同步的方式移动，尽管最初它们被正确地形成和极化。这些缺陷是生殖系自主的，不依赖于 PCP 基因，并且可以被野生型 Cmb 拯救，但不能被已知 Rho 激酶磷酸化位点发生突变的 Cmb 拯救。此外，Cmb 与轴丝成分径向辐条蛋白 3 结合，敲低该蛋白会导致类似的个体化缺陷，表明 Cmb 将个体化机制与微管轴丝协调起来。
