Anatomy and Cell Biology, East Carolina University, Brody School of Medicine, 600 Moye Blvd, Greenville, NC, 27834, USA.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):51-55. doi: 10.1016/j.bbrc.2018.05.170. Epub 2018 Jun 6.
Male germ cells are transformed from undifferentiated stem cells into spermatozoa through a series of highly regulated steps together termed spermatogenesis. Spermatogonial stem cells undergo mitosis and differentiation followed by two rounds of meiotic division and then proceed through a series of dramatic cell shape changes to form highly differentiated spermatozoa. Using indirect immunofluorescence, we investigated a role for the mitotic kinase, Aurora A (AURKA), in these events through localization of this protein in mouse testis and spermatozoa. AURKA is expressed in several cell types in the testis. Spermatogonia and spermatocytes express AURKA as expected based on the known role of this kinase in cell division. Surprisingly, we also found AURKA localized to spermatids and the flagellum of spermatozoa. Total AURKA and activated AURKA are expressed in different compartments of the sperm flagellum with total AURKA found in the principal piece and its phosphorylated and activated form found in the sperm midpiece. In addition, active AURKA is enriched in the flagellum of motile sperm isolated from cauda epididymis. These results provide evidence for a unique role for AURKA in spermatogenesis and sperm motility. Defining the signaling mechanisms that govern spermatogenesis and sperm cell function is crucial to understanding and treating male infertility as well as for development of new contraceptive strategies.
雄性生殖细胞通过一系列高度调控的步骤从未分化的干细胞转变为精子,这些步骤统称为精子发生。精原干细胞经历有丝分裂和分化,随后进行两轮减数分裂,然后通过一系列剧烈的细胞形态变化,形成高度分化的精子。我们通过间接免疫荧光法研究了有丝分裂激酶 Aurora A(AURKA)在这些事件中的作用,方法是定位这种蛋白质在小鼠睾丸和精子中的位置。AURKA 在睾丸中的几种细胞类型中表达。精原细胞和精母细胞表达 AURKA,这与该激酶在细胞分裂中的已知作用一致。令人惊讶的是,我们还发现 AURKA 定位于精子细胞和精子的鞭毛。总 AURKA 和激活的 AURKA 在精子鞭毛的不同部位表达,总 AURKA 存在于主段,其磷酸化和激活形式存在于精子中段。此外,活性 AURKA 在从附睾尾部分离的运动精子的鞭毛中富集。这些结果为 AURKA 在精子发生和精子运动中的独特作用提供了证据。定义调控精子发生和精子细胞功能的信号机制对于理解和治疗男性不育症以及开发新的避孕策略至关重要。