Multiple phosphorylations control recruitment of the KMN network onto kinetochores

• DOI: 10.1038/s41556-018-0230-0
• Publication Date: 2018-11-08T10:16:55Z
• Authors: Masatoshi Hara; Mariko Ariyoshi; Ei-ichi Okumura; Tetsuya Hori; Tatsuo Fukagawa
• Keywords: 0301 basic medicine; Chromosomal Proteins, Non-Histone; Centromere; Mitosis; Spindle Apparatus; Microtubules; 03 medical and health sciences; Cell Line, Tumor; Multiprotein Complexes; Animals; Phosphorylation; Kinetochores; Chickens; Microtubule-Associated Proteins; Protein Binding; Signal Transduction

To establish a functional kinetochore, the constitutive centromere-associated network (CCAN) forms a foundation on the centromere and recruits the KMN network, which directly binds to spindle microtubules. The CENP-C and CENP-T pathways in the CCAN recruit the KMN network to kinetochores, independently. The CENP-C pathway has been considered the major scaffold for the KMN network in vertebrate CCAN. However, we demonstrate that it is mainly the CENP-T pathway that recruits the KMN network onto the kinetochores and that CENP-T-KMN interactions are essential in chicken DT40 cells. By contrast, less Ndc80 binds to the CENP-C pathway in mitosis and the Mis12-CENP-C association is decreased during mitotic progression, which is consistent with the finding that the Mis12 complex-CENP-C binding is dispensable for cell viability. Furthermore, we find that multiple phosphoregulations of CENP-T and the Mis12 complex make the CENP-T pathway dominant. These results provide key insights into kinetochore dynamics during mitotic progression.