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CDC42 驱动 RHOA 活性和肌动蛋白聚合在获能过程中。

CDC42 drives RHOA activity and actin polymerization during capacitation.

机构信息

Departamento de Biología Celular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, San Pedro Zacatenco, Gustavo A. Madero, México City, México.

Universidad Autónoma Benito Juárez de Oaxaca, Facultad de Medicina y Cirugía, Oaxaca, Oaxaca, México.

出版信息

Reproduction. 2020 Sep;160(3):393-404. doi: 10.1530/REP-19-0577.

DOI:10.1530/REP-19-0577
PMID:32567555
Abstract

Mammalian sperm cells acquire fertilizing capacity as a result of a process termed capacitation. Actin polymerization is important for capacitation; inhibiting actin polymerization prevents the adhesion and fusion of the sperm with the ovule. The main function of RHO proteins CDC42 and RHOA is to direct actin polymerization. Although these two RHO proteins are present in mammalian sperm, little is known about their role in capacitation, the acrosome reaction, and the way in which they direct actin polymerization. The purpose of this study was to determine the participation of CDC42 and RHOA in capacitation and the acrosome reaction and their relationship with actin polymerization using guinea pig sperm. Our results show that the inhibition of CDC42 and RHOA alters the kinetics of actin polymerization, capacitation, and the acrosome reaction in different ways. Our results also show that the initiation of actin polymerization and RHOA activation depend on the activation of CDC42 and that RHOA starts its activity and effect on actin polymerization when CDC42 reaches its maximum activity. Given that the inhibition of ROCK1 failed to prevent the acrosomal reaction, the participation of RHOA in capacitation and the acrosomal reaction is independent of its kinase 1 (ROCK1). In general, our results indicate that CDC42 and RHOA have different roles in capacitation and acrosomal reaction processes and that CDC42 plays a preeminent role.

摘要

哺乳动物精子细胞通过一种称为获能的过程获得受精能力。肌动蛋白聚合对于获能很重要;抑制肌动蛋白聚合会阻止精子与卵子的黏附和融合。CDC42 和 RHOA 这两种 RHO 蛋白的主要功能是指导肌动蛋白聚合。尽管这两种 RHO 蛋白存在于哺乳动物精子中,但它们在获能、顶体反应中的作用以及它们指导肌动蛋白聚合的方式知之甚少。本研究旨在使用豚鼠精子确定 CDC42 和 RHOA 在获能和顶体反应中的参与及其与肌动蛋白聚合的关系。我们的结果表明,CDC42 和 RHOA 的抑制以不同的方式改变肌动蛋白聚合、获能和顶体反应的动力学。我们的结果还表明,肌动蛋白聚合的起始和 RHOA 的激活依赖于 CDC42 的激活,并且当 CDC42 达到最大活性时,RHOA 开始其对肌动蛋白聚合的活性和作用。由于 ROCK1 的抑制未能阻止顶体反应,因此 RHOA 参与获能和顶体反应与其激酶 1(ROCK1)无关。总的来说,我们的结果表明,CDC42 和 RHOA 在获能和顶体反应过程中具有不同的作用,而 CDC42 起着突出的作用。

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