RAC1 controls progressive movement and competitiveness of mammalian spermatozoa

by Alexandra Amaral, Bernhard G. Herrmann

Mammalian spermatozoa employ calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) signaling in generating flagellar beat. However, how sperm direct their movement towards the egg cells has remained elusive. Here we show that the Rho small G protein RAC1 plays an important role in controlling progressive motility, in particular average path velocity and linearity. Upon RAC1 inhibition of wild type sperm with the drug NSC23766, progressive movement is impaired. Moreover, sperm from mice homozygous for the genetically variantt-haplotype region (tw5/tw32), which are sterile, show strongly enhanced RAC1 activity in comparison to wild type (+/+) controls, and quickly become immotilein vitro. Sperm from heterozygous (t/+) males, on the other hand, display intermediate RAC1 activity, impaired progressive motility and transmission ratio distortion (TRD) in favor oft-sperm. We show thatt/+-derived sperm consist of two subpopulations, highly progressive and less progressive. The majority of highly progressive sperm carry thet-haplotype, while most less progressive sperm contain the wild type (+) chromosome. Dosage-controlled RAC1 inhibition int/+ sperm by NSC23766 rescues progressive movement of (+)-spermin vitro, directly demonstrating that impairment of progressive motility in the latter is caused by enhanced RAC1 activity. The combined data show that RAC1 plays a pivotal role in controlling progressive motility in sperm, and that inappro...

Source: PLoS Genetics - February 4, 2021 Category: Genetics & Stem Cells Authors: Alexandra Amaral Source Type: research