Phosphorylation of the Anaphase Promoting Complex activator FZR1/CDH1 is required for Meiosis II entry in mouse male germ cell
| Autor: | Kaho Okamura, Kimi Araki, Masatake Araki, Kazumasa Takemoto, Shinji Kuninaka, Kei-ichiro Ishiguro, Sayoko Fujimura, Hideyuki Saya, Naoki Takeda, Nobuhiro Tanno |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Cell division Germline development Somatic cell Ubiquitin-Protein Ligases lcsh:Medicine Cell Cycle Proteins Biology Anaphase-Promoting Complex-Cyclosome Cdh1 Proteins Article Mice Mitotic cell cycle Meiosis medicine Animals Gene Knock-In Techniques Phosphorylation Spermatogenesis lcsh:Science Multidisciplinary Meiosis II lcsh:R Cell cycle Spermatogonia Cell biology Mice Inbred C57BL Germ Cells medicine.anatomical_structure lcsh:Q Anaphase-promoting complex Germ cell |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | FZR1/CDH1 is an activator of Anaphase promoting complex/Cyclosome (APC/C), best known for its role as E3 ubiquitin ligase that drives the cell cycle. APC/C activity is regulated by CDK-mediated phosphorylation of FZR1 during mitotic cell cycle. Although the critical role of FZR1 phosphorylation has been shown mainly in yeast and in vitro cell culture studies, its biological significance in mammalian tissues in vivo remained elusive. Here, we examined the in vivo role of FZR1 phosphorylation using a mouse model, in which non-phosphorylatable substitutions were introduced in the putative CDK-phosphorylation sites of FZR1. Although ablation of FZR1 phosphorylation did not show substantial consequences in mouse somatic tissues, it led to severe testicular defects resulting in male infertility. In the absence of FZR1 phosphorylation, male juvenile germ cells entered meiosis normally but failed to enter meiosis II or form differentiated spermatids. In aged testis, male mutant germ cells were overall abolished, showing Sertoli cell-only phenotype. In contrast, female mutants showed apparently normal progression of meiosis. The present study demonstrated that phosphorylation of FZR1 is required for temporal regulation of APC/C activity at meiosis II entry, and for maintenance of spermatogonia, which raised an insight into the sexual dimorphism of FZR1-regulation in germ cells. |
| Databáze: | OpenAIRE |
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