LRRC45 is a centrosome linker component required for centrosome cohesion

Area of Science:

• Cell Biology
• Molecular Biology
• Centrosome Biology

Background:

• Centrosomes function as a single microtubule-organizing center via a proteinaceous linker.
• The composition and regulation of this centrosomal linker are largely unknown.

Purpose of the Study:

• To identify the molecular components of the centrosome linker.
• To elucidate the regulatory mechanisms governing centrosome cohesion and separation.

Main Methods:

• Immunofluorescence microscopy to determine LRRC45 localization.
• RNA interference (RNAi) to deplete LRRC45.
• Co-immunoprecipitation to study protein interactions.
• Phosphorylation site analysis.

Main Results:

• LRRC45 localizes to the proximal ends of centrioles, forming fiber-like structures.
• LRRC45 depletion causes centrosome splitting during interphase.
• LRRC45 interacts with C-Nap1 and rootletin.
• Nek2A-mediated phosphorylation of LRRC45 at S661 during mitosis reduces its localization and fiber formation, leading to centrosome separation.

Conclusions:

• LRRC45 is a critical component of the intercentriolar linker, essential for centrosome cohesion.
• LRRC45 function and localization are regulated by Nek2A-mediated phosphorylation during mitosis, controlling centrosome separation.