Activating adaptor-like sequences in pericentrin mediate its transport by dynein

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Abstract

Right before a cell divides, the centrosome rapidly increases its size and microtubule organizing activity through a process termed centrosome maturation. PCNT, a coiled-coil centrosomal protein, is synthesized and transported to the centrosome simultaneously by dynein. This dynein-mediated co-translational transport of PCNT facilitates centrosome maturation and mitotic spindle formation. How dynein engages and transports PCNT, however, remains unclear. Here we find that PCNT residues 1393–1525 are required for mediating dynein-dynactin interaction. PCNT (1393–1525) also shares similar sequence features with canonical dynein cargo adaptors. PCNT is predicted to interact with dynein heavy chains through similar contact sites used by canonical dynein cargo adaptors. Introducing point mutations at those contact sites abolishes dyneinmediated transport in a peroxisome motility assay. Our results suggest that PCNT contains adaptorlike sequences to bind and activate dynein directly during its transport to the centrosome. Our data also suggest that dynein may engage with some of its cargoes directly without an adaptor.

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