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

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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.1005485

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1. Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell. 1983;33(2):389–96. 6134587

2. Loyer P, Trembley JH, Katona R, Kidd VJ, Lahti JM. Role of CDK/cyclin complexes in transcription and RNA splicing. Cell Signal. 2005;17(9):1033–51. 15935619

3. Mikolcevic P, Rainer J, Geley S. Orphan kinases turn eccentric: a new class of cyclin Y-activated, membrane-targeted CDKs. Cell Cycle. 2012;11(20):3758–68. doi: 10.4161/cc.21592 22895054

4. Liu D, Finley RL Jr. Cyclin Y is a novel conserved cyclin essential for development in Drosophila. Genetics. 2010;184(4):1025–35. doi: 10.1534/genetics.110.114017 20100936

5. Mikolcevic P, Sigl R, Rauch V, Hess MW, Pfaller K, Barisic M, et al. Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis. Mol Cell Biol. 2012;32(4):868–79. doi: 10.1128/MCB.06261-11 22184064

6. Davidson G, Shen J, Huang YL, Su Y, Karaulanov E, Bartscherer K, et al. Cell cycle control of wnt receptor activation. Dev Cell. 2009;17(6):788–99. doi: 10.1016/j.devcel.2009.11.006 20059949

7. Hartwell LH. Saccharomyces cerevisiae cell cycle. Bacteriol Rev. 1974;38(2):164–98. 4599449

8. Solomon MJ. Activation of the various cyclin/cdc2 protein kinases. Curr Opin Cell Biol. 1993;5(2):180–6. 8507489

9. Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J Mol Biol. 1999;287(5):821–8. 10222191

10. Okuda T, Cleveland JL, Downing JR. PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein kinase gene family. Oncogene. 1992;7(11):2249–58. 1437147

11. Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 2013;140(15):3079–93. doi: 10.1242/dev.091744 23861057

12. Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, et al. A family of human cdc2-related protein kinases. EMBO J. 1992;11(8):2909–17. 1639063

13. Besset V, Rhee K, Wolgemuth DJ. The cellular distribution and kinase activity of the Cdk family member Pctaire1 in the adult mouse brain and testis suggest functions in differentiation. Cell Growth Differ. 1999;10(3):173–81. 10099831

14. Charrasse S, Carena I, Hagmann J, Woods-Cook K, Ferrari S. PCTAIRE-1: characterization, subcellular distribution, and cell cycle-dependent kinase activity. Cell Growth Differ. 1999;10(9):611–20. 10511311

15. Graeser R, Gannon J, Poon RY, Dubois T, Aitken A, Hunt T. Regulation of the CDK-related protein kinase PCTAIRE-1 and its possible role in neurite outgrowth in Neuro-2A cells. J Cell Sci. 2002;115(Pt 17):3479–90. 12154078

16. Shimizu K, Uematsu A, Imai Y, Sawasaki T. Pctaire1/Cdk16 promotes skeletal myogenesis by inducing myoblast migration and fusion. FEBS Lett. 2014;588(17):3030–7. doi: 10.1016/j.febslet.2014.05.060 24931367

17. Liu Y, Cheng K, Gong K, Fu AK, Ip NY. Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein: implications in the regulation of its hexamerization and exocytosis. J Biol Chem. 2006;281(15):9852–8. 16461345

18. Palmer KJ, Konkel JE, Stephens DJ. PCTAIRE protein kinases interact directly with the COPII complex and modulate secretory cargo transport. J Cell Sci. 2005;118(Pt 17):3839–47. 16091426

19. Oakberg EF. Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat. 1956;99(3):507–16. 13402729

20. Bastos H, Lassalle B, Chicheportiche A, Riou L, Testart J, Allemand I, et al. Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis. Cytometry A. 2005;65(1):40–9. 15779065

21. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. A conditional knockout resource for the genome-wide study of mouse gene function. Nature. 2011;474(7351):337–42. doi: 10.1038/nature10163 21677750

22. Semenov MV, Habas R, Macdonald BT, He X. SnapShot: Noncanonical Wnt Signaling Pathways. Cell. 2007;131(7):1378. 18160045

23. Jeffrey PD, Russo AA, Polyak K, Gibbs E, Hurwitz J, Massague J, et al. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature. 1995;376(6538):313–20. 7630397

24. Russo AA, Jeffrey PD, Pavletich NP. Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat Struct Biol. 1996;3(8):696–700. 8756328

25. Wolgemuth DJ, Manterola M, Vasileva A. Role of cyclins in controlling progression of mammalian spermatogenesis. Int J Dev Biol. 2013;57(2–4):159–68. doi: 10.1387/ijdb.130047av 23784826

26. Yu Q, Wu J. Involvement of cyclins in mammalian spermatogenesis. Mol Cell Biochem. 2008;315(1–2):17–24. doi: 10.1007/s11010-008-9783-8 18470654

27. Liu D, Matzuk MM, Sung WK, Guo Q, Wang P, Wolgemuth DJ. Cyclin A1 is required for meiosis in the male mouse. Nat Genet. 1998;20(4):377–80. 9843212

28. Jiang M, Gao Y, Yang T, Zhu X, Chen J. Cyclin Y, a novel membrane-associated cyclin, interacts with PFTK1. FEBS Lett. 2009;583(13):2171–8. doi: 10.1016/j.febslet.2009.06.010 19524571

29. Kissel H, Georgescu MM, Larisch S, Manova K, Hunnicutt GR, Steller H. The Sept4 septin locus is required for sperm terminal differentiation in mice. Dev Cell. 2005;8(3):353–64. 15737931

30. Ihara M, Kinoshita A, Yamada S, Tanaka H, Tanigaki A, Kitano A, et al. Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa. Dev Cell. 2005;8(3):343–52. 15737930

31. Olson GE, Winfrey VP, Nagdas SK, Hill KE, Burk RF. Selenoprotein P is required for mouse sperm development. Biol Reprod. 2005;73(1):201–11. 15744015

32. Toure A, Lhuillier P, Gossen JA, Kuil CW, Lhote D, Jegou B, et al. The testis anion transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse. Hum Mol Genet. 2007;16(15):1783–93. 17517695

33. Zheng H, Stratton CJ, Morozumi K, Jin J, Yanagimachi R, Yan W. Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility. Proc Natl Acad Sci U S A. 2007;104(16):6852–7. 17426145

34. Miller ME, Cross FR. Cyclin specificity: how many wheels do you need on a unicycle? J Cell Sci. 2001;114(Pt 10):1811–20. 11329367

35. Breucker H, Schafer E, Holstein AF. Morphogenesis and fate of the residual body in human spermiogenesis. Cell Tissue Res. 1985;240(2):303–9. 3995554

36. Blanco-Rodriguez J, Martinez-Garcia C. Apoptosis is physiologically restricted to a specialized cytoplasmic compartment in rat spermatids. Biol Reprod. 1999;61(6):1541–7. 10570001

37. Toure A, Rode B, Hunnicutt GR, Escalier D, Gacon G. Septins at the annulus of mammalian sperm. Biol Chem. 2011;392(8–9):799–803. doi: 10.1515/BC.2011.074 21740329

38. Amin ND, Zheng YL, Kesavapany S, Kanungo J, Guszczynski T, Sihag RK, et al. Cyclin-dependent kinase 5 phosphorylation of human septin SEPT5 (hCDCrel-1) modulates exocytosis. J Neurosci. 2008;28(14):3631–43. doi: 10.1523/JNEUROSCI.0453-08.2008 18385322

39. Sinha I, Wang YM, Philp R, Li CR, Yap WH, Wang Y. Cyclin-dependent kinases control septin phosphorylation in Candida albicans hyphal development. Dev Cell. 2007;13(3):421–32. 17765684

40. Li CR, Au Yong JY, Wang YM, Wang Y. CDK regulates septin organization through cell-cycle-dependent phosphorylation of the Nim1-related kinase Gin4. J Cell Sci. 2012;125(Pt 10):2533–43. doi: 10.1242/jcs.104497 22366454

41. Zhou Y, Ru Y, Wang C, Wang S, Zhou Z, Zhang Y. Tripeptidyl peptidase II regulates sperm function by modulating intracellular Ca(2+) stores via the ryanodine receptor. PLoS One. 2013;8(6):e66634. doi: 10.1371/journal.pone.0066634 23818952

42. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367–72. doi: 10.1038/nbt.1511 19029910

43. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006;127(3):635–48. 17081983