The CP110-CEP97-CEP290 module orchestrates a centriolar satellite dependent response to proteotoxic stress

Abstract

ABSTRACTProtein degradation at the centrosome, the primary microtubule organizing centre of the cell, is critical to a myriad of cellular processes. Perturbation of the ubiquitin proteasome system causes the formation of an inclusion, or aggresome, at the centrosome. By systematic microscopy analysis, we have placed a subset of centrosomal proteins within the aggresome. Centriolar satellites, proteinaceous granules found in the vicinity of centrosomes, also became incorporated into this structure. Through high-resolution quantitative analysis, we have defined aggresome assembly at the centrosome, demonstrating a requirement for satellites in this process. Furthermore, a module consisting of CP110-CEP97-CEP290 was required to recruit aggresome components early in the pathway and senescent cells were defective in aggresome formation due to limiting amounts of CP110. Finally, satellites and the CP110-CEP97-CEP290 module were required for the aggregation of mutant huntingtin. The accumulation of protein aggregates is central to the pathology of a range of human disorders. These data thereby reveal new roles for CP110, its interactors, and centriolar satellites in controlling cellular proteostasis and the aggregation of disease relevant proteins.