Pericentrin contains internal adaptor-like sequences that activate dynein directly

Abstract

Centrosome maturation, the rapid growth of the centrosome before cell division, prepares the cell for spindle assembly. Pericentrin (PCNT), a coiled-coil centrosomal protein, is transported to the centrosome by dynein during its translation, and this co-translational transport promotes maturation. How dynein engages PCNT remains unclear. We show that PCNT residues 1393-1525 are required for the dynein-dynactin interaction. This region shares bulk sequence features with canonical dynein cargo adaptors, and three of five synthetic sequences matching these features fully or partially restored transport of a PCNT variant lacking residues 1393-1525. PCNT is predicted to contact dynein heavy chain at sites used by canonical adaptors, and mutating these sites abolished transport. Purified PCNT activated dynein-dynactin directly without additional factors. These results suggest that PCNT binds and activates dynein through an adaptor-like sequence, with no separate adaptor, and that dynein recognizes cargoes by more diverse mechanisms than previously recognized, including an internal rather than N-terminal binding region.