CDK1 and CEP97 cooperatively control centriole length to orchestrate ciliogenesis and developmental patterning.

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Organelle function relies on precise architecture.
• Centrioles, key centrosome components, have tightly regulated lengths.
• Centrosomal protein phosphorylation impacts centriole function.

Purpose of the Study:

• To investigate the role of cyclin-dependent kinase 1 (CDK1) in regulating centriole length.
• To elucidate the mechanisms by which CDK1 and CEP97-CCP110 control centriole elongation.
• To understand the impact of centriole length dysregulation on ciliogenesis and mammalian development.

Main Methods:

• Adapted centrosome purification techniques for phosphoproteomics.
• Performed centrosome-specific phosphoproteomics with and without CDK1 activity.
• Utilized mouse models to assess the in vivo effects of CEP97 removal on development.

Main Results:

• CDK1 phosphorylates numerous centriolar proteins, including Centrobin, affecting centriole length control.
• CDK1 and the CEP97-CCP110 complex synergistically regulate centriole length.
• CEP97 restricts Centrobin localization, while CDK1 phosphorylation suppresses Centrobin's elongation function.
• Overelongated centrioles impair ciliogenesis and disrupt mammalian development, including heart formation.

Conclusions:

• CDK1 and CEP97-CCP110 cooperatively restrict Centrobin function to control centriole length.
• Proper centriole length regulation by these factors is critical for ciliogenesis and mammalian development.
• Dysregulation leads to developmental defects, highlighting the importance of precise centriole architecture.