Dimerization of CPAP orchestrates centrosome cohesion plasticity

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Centrosome cohesion and segregation are vital for accurate cell division and bipolar spindle formation.
• CPAP (Centrosome Protein Associated with Primary Microcephaly) is a centrosome protein involved in brain size control and centriole length regulation.
• Previous research indicates CPAP interacts with tubulin.

Purpose of the Study:

• To investigate the role of CPAP homodimerization in centrosome cohesion and cell cycle regulation.
• To elucidate the mechanism by which CPAP self-interaction is regulated during the cell cycle.
• To understand how CPAP dynamics contribute to genomic stability.

Main Methods:

• Biochemical studies to assess CPAP homodimerization in vivo.
• Analysis of CPAP's coiled-coil domains to identify regions critical for dimerization.
• Investigation of CPAP phosphorylation during mitosis and its effect on intermolecular interactions.

Main Results:

• CPAP forms a homodimer during interphase, mediated by its fifth coiled-coil domain.
• CPAP self-interaction is essential for maintaining centrosome cohesion before the G(2)/M phase.
• CPAP phosphorylation during mitosis disrupts homodimerization, suggesting cell cycle-regulated control.
• Both monomeric and dimeric forms of CPAP are necessary for accurate cell division.

Conclusions:

• CPAP homodimerization is a cell cycle-regulated process crucial for centrosome cohesion.
• Mitotic phosphorylation of CPAP dynamically regulates its interaction state, impacting centrosome splitting.
• These findings highlight the importance of CPAP's molecular dynamics in ensuring genomic stability during cell division.