CCDC74A/B are K-fiber crosslinkers required for chromosomal alignment

• Main Authors: Haining Zhou, Tao Zheng, Tianning Wang, Qi Li, Fulin Wang, Xin Liang, Jianguo Chen, Junlin Teng
• Format: Article
• Language: English
• Published: BMC 2019-09-01
• Series: BMC Biology
• Subjects: CCDC74A; CCDC74B; Kinetochore fiber; Microtubule dynamic; Spindle assembly; Chromosomal alignment
• Online Access: http://link.springer.com/article/10.1186/s12915-019-0694-9

Abstract Background Spindle microtubule organization, regulated by microtubule-associated proteins, is critical for cell division. Proper organization of kinetochore fiber (K-fiber), connecting spindle poles and kinetochores, is a prerequisite for precise chromosomal alignment and faithful genetic material transmission. However, the mechanisms of K-fiber organization and dynamic maintenance are still not fully understood. Results We reveal that two previously uncharacterized coiled-coil domain proteins CCDC74A and CCDC74B (CCDC74A/B) are spindle-localized proteins in mammalian cells. They bind directly to microtubules through two separate domains and bundle microtubules both in vivo and in vitro. These functions are required for K-fiber organization, bipolar spindle formation, and chromosomal alignment. Moreover, CCDC74A/B form homodimers in vivo, and their self-association activity is necessary for microtubule bundling and K-fiber formation. Conclusions We characterize CCDC74A and CCDC74B as microtubule-associated proteins that localize to spindles and are important K-fiber crosslinkers required for bipolar spindle formation and chromosome alignment.