Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites

Prosser et al. report that centriolar satellite and centrosomal proteins seed aggresomes, perinuclear inclusions of misfolded proteins, and may play a role in aggresome formation during senescence and huntingtin aggregation. Protein degradation is critical to maintaining cellular homeostasis, and perturbation of the ubiquitin proteasome system leads to the accumulation of protein aggregates. These aggregates are either directed towards autophagy for destruction or sequestered into an inclusion, termed the aggresome, at the centrosome. Utilizing high-resolution quantitative analysis, here, we define aggresome assembly at the centrosome in human cells. Centriolar satellites are proteinaceous granules implicated in the trafficking of proteins to the centrosome. During aggresome assembly, satellites were required for the growth of the aggresomal structure from an initial ring of phosphorylated HSP27 deposited around the centrioles. The seeding of this phosphorylated HSP27 ring depended on the centrosomal proteins CP110, CEP97 and CEP290. Owing to limiting amounts of CP110, senescent cells, which are characterized by the accumulation of protein aggregates, were defective in aggresome formation. Furthermore, satellites and CP110-CEP97-CEP290 were required for the aggregation of mutant huntingtin. Together, these data reveal roles for CP110-CEP97-CEP290 and satellites in the control of cellular proteostasis and the aggregation of disease-relevant proteins.

Automated summary

In this study, the researchers found that centriolar satellite and centrosomal proteins are crucial for the formation of aggresomes and the aggregation of disease-relevant proteins. They showed that satellites are required for the growth of aggresomal structure and this growth depends on the centrosomal proteins CP110, CEP97, and CEP290.