CLIP-170 is required to recruit PLK1 to kinetochores during early mitosis for chromosome alignment

Abstract

The cytoplasmic linker protein (CLIP)-170, an outer kinetochore protein, has a role in kinetochore–microtubule attachment and chromosome alignment during mitosis. However, the mechanism of CLIP-170's involvement in chromosome alignment is not known. Here we show that CLIP-170 co-localizes with Polo-like kinase 1 (PLK1) at kinetochores during early mitosis. Depletion of CLIP-170 results in a significant reduction of PLK1 recruitment to kinetochores, and causes kinetochore-fiber (K-fiber) instability and defects in chromosome alignment at the metaphase plate. These phenotypes are dependent on the phosphorylation of CLIP-170 at a CDK1-site, T287, as ectopic expression of wild-type CLIP-170, but not non-phosphorylatable mutant, CLIP-170–T287A, restores PLK1 localization at kinetochores and rescues K-fiber stability and chromosome alignment. These data suggest that CLIP-170 acts as a novel recruiter and spatial regulator of PLK1 at kinetochores during early mitosis, to promote K-fiber stability and chromosome alignment for error-free chromosome segregation.