GSK3-mediated CLASP2 phosphorylation modulates kinetochore dynamics

Error-free chromosome segregation requires dynamic control of microtubule attachment to kinetochores, but how kinetochore-microtubule interactions are spatially and temporally controlled during mitosis remains incompletely understood. In addition to the NDC80 microtubule-binding complex, other proteins with demonstrated microtubule-binding activities localize to kinetochores. One such protein is the cytoplasmic linker-associated protein 2 (CLASP2). Here, we show that global GSK3-mediated phosphorylation of the longest isoform, CLASP2 alpha, largely abolishes CLASP2 alpha-microtubule association in metaphase. However, it does not directly control localization of CLASP2 alpha to kinetochores. Using dominant phosphorylation-site variants, we find that CLASP2 alpha phosphorylation weakens kinetochore-microtubule interactions as evidenced by decreased tension between sister kinetochores. Expression of CLASP2 alpha phosphorylation-site mutants also resulted in increased chromosome segregation defects, indicating that GSK3-mediated control of CLASP2 alpha-microtubule interactions contributes to correct chromosome dynamics. Because of global inhibition of CLASP2 alpha-microtubule interactions, we propose a model in which only kinetochore-bound CLASP2 alpha is dephosphorylated, locally engaging its microtubule-binding activity.