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

Area of Science:

• Reproductive Biology
• Molecular Cell Biology
• Biochemistry

Background:

• Cyclin Y-like 1 (Ccnyl1) is a novel cyclin family member with limited functional characterization.
• Cyclin Y (Ccny) shares high sequence similarity with Ccnyl1, but its role in fertility is distinct.

Purpose of the Study:

• To elucidate the function of Ccnyl1 in mammalian reproduction.
• To investigate the molecular mechanisms underlying Ccnyl1's role in male fertility.

Main Methods:

• Generation and phenotypic analysis of Ccnyl1 knockout mice.
• Sperm analysis including motility and morphology assessment.
• Co-immunoprecipitation and Western blotting to study protein interactions and stability.
• Kinase activity assays and mass spectrometry for phosphorylation site identification.

Main Results:

• Ccnyl1 is highly expressed in mouse testes and is crucial for male fertility; Ccnyl1 knockout mice are infertile.
• Sperm from Ccnyl1-/- mice exhibit impaired motility and structural defects.
• Ccnyl1 interacts with and stabilizes cyclin-dependent kinase 16 (CDK16), enhancing its kinase activity.
• Specific N-terminal phosphorylation sites on CDK16 are critical for Ccnyl1 binding and kinase modulation.

Conclusions:

• Ccnyl1 plays an indispensable role in male spermatogenesis.
• Ccnyl1 regulates male fertility through interaction with and modulation of CDK16 activity and stability.
• Understanding Ccnyl1-CDK16 interaction provides insights into male infertility mechanisms.