Dynamic SAS-6 phosphorylation aids centrosome duplication and elimination in C. elegans oogenesis

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Biology

Background:

• Centrosome elimination in oogenesis is vital for accurate centriole inheritance in metazoans.
• The molecular mechanisms governing centrosome dynamics and elimination during oogenesis are not fully understood.

Purpose of the Study:

• To elucidate the role of SAS-6 phosphorylation in controlling centrosome dynamics during oogenesis.
• To identify the kinase responsible for SAS-6 phosphorylation and its functional consequences.

Main Methods:

• In vitro phase separation assays of purified SAS-6.
• Cellular overexpression of SAS-6 and analysis of droplet formation.
• Mass spectrometry and kinase assays to identify SAS-6 phosphorylation sites and kinases.
• Analysis of phospho-mimetic and phospho-deficient SAS-6 mutants.
• Assessment of centriole disassembly and SAS-6 degradation.

Main Results:

• SAS-6 undergoes dynamic behavior and phase separation in vitro and in cells.
• CDK-1 directly phosphorylates SAS-6 at its C-terminus, inhibiting phase separation and protein interactions.
• SAS-6 degradation is linked to centrosome stability, and CDK-1 activity is essential for centriole disassembly.
• Dynamic SAS-6 phosphorylation is critical for both centrosome assembly and elimination during oogenesis.

Conclusions:

• Controlled SAS-6 phosphorylation by CDK-1 is a key regulatory mechanism for centrosome dynamics during oogenesis.
• Phosphorylation disrupts SAS-6 multivalent interactions, impacting centriole stability and promoting elimination.
• This study reveals a novel mechanism for regulating centriole inheritance through dynamic control of SAS-6 phosphorylation.