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Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis

Petra Mikolcevic1, Reinhard Sigl, Veronika Rauch

  • 1Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.

Molecular and Cellular Biology
|December 21, 2011
PubMed

Insights

Cyclin-dependent kinase 16 (CDK16) is activated by cyclin Y (CCNY) and is crucial for male fertility. CDK16 deficiency in mice leads to infertility due to defects in sperm structure and motility.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Reproductive Biology

Background:

  • Cyclin-dependent kinase 16 (CDK16) is a poorly understood protein kinase with high expression in the testis and brain.
  • Its regulatory mechanisms and in vivo functions remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the activation mechanism of CDK16 by its associated cyclin Y (CCNY).
  • To investigate the physiological role of CDK16 in vivo, particularly in spermatogenesis.

Main Methods:

  • Utilized transfected human cells to study CDK16-CCNY interaction and membrane targeting.
  • Employed forskolin (PKA activator) and kinase inhibitors to modulate CDK16 localization.
  • Generated and analyzed CDK16 conditional knockout mice to assess in vivo function.
  • Examined sperm morphology, motility, and structural integrity in CDK16-deficient males.

Main Results:

  • CDK16 is activated by membrane-associated cyclin Y (CCNY).
  • CCNY binding to CDK16 is regulated by phosphorylation at serine 153, a potential PKA site.
  • CDK16 knockout male mice exhibit infertility with severe defects in sperm annulus, shape, motility, head formation, and residual cytoplasm.
  • These defects suggest a critical role for CDK16 in spermiation.

Conclusions:

  • CDK16 is a membrane-targeted CDK regulated by phosphorylation-controlled cyclin binding.
  • CDK16 plays an essential role in spermatogenesis and is vital for male fertility.

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