CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse

PLoS Genet. 2015 Aug 25;11(8):e1005485. doi: 10.1371/journal.pgen.1005485. eCollection 2015 Aug.

Abstract

Cyclin Y-like 1 (Ccnyl1) is a newly-identified member of the cyclin family and is highly similar in protein sequences to Cyclin Y (Ccny). However, the function of Ccnyl1 is poorly characterized in any organism. Here we found that Ccnyl1 was most abundantly expressed in the testis of mice and was about seven times higher than the level of Ccny. Male Ccnyl1-/- mice were infertile, whereas both male and female Ccny-/- mice displayed normal fertility. These results suggest that Ccnyl1, but not Ccny, is indispensable for male fertility. Spermatozoa obtained from Ccnyl1-/- mice displayed significantly impaired motility, and represented a thinned annulus region and/or a bent head. We found that the protein, but not the mRNA, level of cyclin-dependent kinase 16 (CDK16) was decreased in the testis of Ccnyl1-/- mice. Further study demonstrated that CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins. Moreover, the interaction increased the kinase activity of CDK16. In addition, we observed an alteration of phosphorylation levels of CDK16 in the presence of CCNYL1. We identified the phosphorylation sites of CDK16 by mass spectrometry and revealed that several phosphorylation modifications on the N-terminal region of CDK16 were indispensable for the CCNYL1 binding and the modulation of CDK16 kinase activity. Our results therefore reveal a previously unrecognized role of CCNYL1 in regulating spermatogenesis through the interaction and modulation of CDK16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinases / physiology*
  • Cyclins / metabolism*
  • Cyclins / physiology*
  • Female
  • Fertility
  • Gene Expression
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Stability
  • Sperm Motility
  • Spermatogenesis*

Substances

  • Ccnyl1 protein, mouse
  • Cyclins
  • cyclin Y, mouse
  • Cyclin-Dependent Kinases
  • PCTAIRE-1 protein kinase

Grant support

This work was supported by grants to JW from the National Natural Science Foundation of China (31130034 and 31470808) and from the Science and Technology Commission of Shanghai Municipality (13DZ1940100), and to WWS from the National Natural Science Foundation of China (31471370) and the Start-up Fund of ShanghaiTech University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.