4.4 Article

Mob4 is essential for spermatogenesis in Drosophila melanogaster

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GENETICS
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GENETICS SOCIETY AMERICA
DOI: 10.1093/genetics/iyad104

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Mob4; axoneme; spermiogenesis; male fertility; STRIPAK complex

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This study reveals the essential role of the Mob4 gene in male fertility in Drosophila melanogaster. Mob4 is required for proper axonemal structure and is necessary for spermatid individualization and the presence of mature sperm in the seminal vesicles. The findings suggest that Mob4 is evolutionarily and functionally conserved and contributes to the regulation of the microtubule- and actin-cytoskeleton during spermatogenesis through the STRIPAK complex.
Gamete formation is essential for sexual reproduction in metazoans. Meiosis in males gives rise to spermatids that must differentiate and individualize into mature sperm. In Drosophila melanogaster, individualization of interconnected spermatids requires the formation of individualization complexes that synchronously move along the sperm bundles. Here, we show that Mob4, a member of the Mps-one binder family, is essential for male fertility but has no detectable role in female fertility. We show that Mob4 is required for proper axonemal structure and its loss leads to male sterility associated with defective spermatid individualization and absence of mature sperm in the seminal vesicles. Transmission electron micrographs of developing spermatids following mob4(RNAi) revealed expansion of the outer axonemal microtubules such that the 9 doublets no longer remained linked to each other and defective mitochondrial organization. Mob4 is a STRIPAK component, and male fertility is similarly impaired upon depletion of the STRIPAK components, Strip and Cka. Expression of the human Mob4 gene rescues all phenotypes of Drosophila mob4 downregulation, indicating that the gene is evolutionarily and functionally conserved. Together, this suggests that Mob4 contributes to the regulation of the microtubule- and actin-cytoskeleton during spermatogenesis through the conserved STRIPAK complex. Our study advances the understanding of male infertility by uncovering the requirement for Mob4 in sperm individualization.

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