CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments

• Published in: The Journal of cell biology Vol. 219; no. 2; p. jcb.201905080
• Main Authors: Girão, Hugo, Okada, Naoyuki, Rodrigues, Tony A, Silva, Alexandra O, Figueiredo, Ana C, Garcia, Zaira, Moutinho-Santos, Tatiana, Hayashi, Ikuko, Azevedo, Jorge E, Macedo-Ribeiro, Sandra, Maiato, Helder
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 03.02.2020
• Subjects: Binding; Chromosomes; Depolymerization; Disasters; Domains; Fasteners; Kinetochores; Localization; Mitosis; Proteins; Self-association
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201905080

CLASPs are conserved microtubule plus-end-tracking proteins that suppress microtubule catastrophes and independently localize to kinetochores during mitosis. Thus, CLASPs are ideally positioned to regulate kinetochore-microtubule dynamics required for chromosome segregation fidelity, but the underlying mechanism remains unknown. Here, we found that human CLASP2 exists predominantly as a monomer in solution, but it can self-associate through its C-terminal kinetochore-binding domain. Kinetochore localization was independent of self-association, and driving monomeric CLASP2 to kinetochores fully rescued normal kinetochore-microtubule dynamics, while partially sustaining mitosis. CLASP2 kinetochore localization, recognition of growing microtubule plus-ends through EB-protein interaction, and the ability to associate with curved microtubule protofilaments through TOG2 and TOG3 domains independently sustained normal spindle length, timely spindle assembly checkpoint satisfaction, chromosome congression, and faithful segregation. Measurements of kinetochore-microtubule half-life and poleward flux revealed that CLASP2 regulates kinetochore-microtubule dynamics by integrating distinctive microtubule-binding properties at the kinetochore-microtubule interface. We propose that kinetochore CLASP2 suppresses microtubule depolymerization and detachment by binding to curved protofilaments at microtubule plus-ends.