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A Conserved Requirement for Fbxo7 During Male Germ Cell Cytoplasmic Remodeling

Rathje, Claudia C and Randle, Suzanne J and Al Rawi, Sara and Skinner, Benjamin M and Nelson, David E and Majumdar, Antara and Johnson, Emma EP and Bacon, Joanne and Vlazaki, Myrto and Affara, Nabeel A and Ellis, Peter J and Laman, Heike (2019) 'A Conserved Requirement for Fbxo7 During Male Germ Cell Cytoplasmic Remodeling.' Frontiers in Physiology, 10. 1278-. ISSN 1664-042X

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Fbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here, we show that in addition to the previously known Parkinsonian and hematopoietic phenotypes, male mice with reduced Fbxo7 expression are sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the spermatids undergo cytoplasmic remodeling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7 mutant males. Mutation of the Drosophila Fbxo7 ortholog, nutcracker (ntc) also leads to sterility with germ cell death during cytoplasmic remodeling, indicating that the requirement for Fbxo7 at this stage is conserved. The ntc phenotype was attributed to decreased levels of the proteasome regulator, DmPI31 and reduced proteasome activity. Consistent with the fly model, we observe a reduction in PI31 levels in mutant mice; however, there is no alteration in proteasome activity in whole mouse testes. Our results are consistent with findings that Fbxo7 regulates PI31 protein levels, and indicates that a defect at the late stages of spermiogenesis, possibly due to faulty spatial dynamics of proteasomes during cytoplasmic remodeling, may underlie the fertility phenotype in mice.

Item Type: Article
Uncontrolled Keywords: Fbxo7, PI31, proteasome, spermatogenesis, cell remodeling, germ cell
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 18 Oct 2019 13:24
Last Modified: 18 Aug 2022 12:31

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