SKAP interacts with Aurora B to guide end-on capture of spindle microtubules via phase separation

• 作者: Manjuan Zhang Fengrui Yang Wenwen Wang Najdat Zohbi Xiwei Wang Dongmei Wang Xiaoxuan Zhuang Zhen Dou Dan Liu Xiaoyu Song Hadiyah-Nicole Green Xing Liu Xuebiao Yao
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（12）
• 所属期刊栏目: Articles
• 页码范围: 841-852
• 页数: 12页
• 语种: 英文
• DOI: 10.1093/jmcb/mjab058

摘要

Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules.Our recent studies show that mitotic motor CENP-E cooperates with SKAP and forms a link between kinetochore core MIS13 complex and spindle microtubule plus-ends to achieve accurate chromosome alignment in mitosis.However,it remains elusive how SKAP regu-lates kinetochore attachment from lateral association to end-on attachment during metaphase alignment.Here,we identify a novel in-teraction between Aurora B and SKAP that orchestrates accurate interaction between the kinetochore and dynamic spindle microtu-bules.Interestingly,SKAP spontaneously phase-separates in vitro via week,multivalent interactions into droplets with fast internal dynamics.SKAP and Aurora B form heterogeneous coacervates in vitro,which recapitulate the dynamics and behavior of SKAP comets in vivo.Importantly,SKAP interaction with Aurora B via phase separation is essential for accurate chromosome segregation and align-ment.Based on those findings,we reason that SKAP-Aurora B interaction via phase separation constitutes a dynamic pool of Aurora B activity during the lateral to end-on conversion of kinetochore-microtubule attachments to achieve faithful cell division.