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CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse
Infertility is a global public health issue that affects up to 15% of reproductive-age couples worldwide, and male infertility contributes to about 50% of these cases. However, our knowledge of the genetic causes of infertility is still limited. Nowadays, the knockout or mutant animal models have become valuable tools for identifying dysfunctional genes in the infertile population. Here, we show that CCNYL1 is specifically and highly expressed in the testis and mainly localized on the plasma membrane of spermatocytes and spermatids. Using the Ccnyl1 knockout model, we found that male but not female Ccnyl1-/ - mice were infertile, accompanied by sperm defects in both motility and structural integrity. Most cyclins are known to function by forming complexes with CDKs, and our study shows for the first time that the partner for CCNYL1 is CDK16. We found that the interaction between CCNYL1 and CDK16 was indispensable for the stability and activity of CDK16. Phosphorylation modifications on CDK16 were also involved in this process. Our study thus reveals an important role of CCNYL1 in regulating male mouse fertility by cooperating with CDK16 and provides insights into the mechanisms underlying cases of male infertility with similar phenotypes.
Vyšlo v časopise: CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005485
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005485Souhrn
Infertility is a global public health issue that affects up to 15% of reproductive-age couples worldwide, and male infertility contributes to about 50% of these cases. However, our knowledge of the genetic causes of infertility is still limited. Nowadays, the knockout or mutant animal models have become valuable tools for identifying dysfunctional genes in the infertile population. Here, we show that CCNYL1 is specifically and highly expressed in the testis and mainly localized on the plasma membrane of spermatocytes and spermatids. Using the Ccnyl1 knockout model, we found that male but not female Ccnyl1-/ - mice were infertile, accompanied by sperm defects in both motility and structural integrity. Most cyclins are known to function by forming complexes with CDKs, and our study shows for the first time that the partner for CCNYL1 is CDK16. We found that the interaction between CCNYL1 and CDK16 was indispensable for the stability and activity of CDK16. Phosphorylation modifications on CDK16 were also involved in this process. Our study thus reveals an important role of CCNYL1 in regulating male mouse fertility by cooperating with CDK16 and provides insights into the mechanisms underlying cases of male infertility with similar phenotypes.
Zdroje
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Štítky
Genetika Reprodukčná medicína
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