Dynamic phosphorylation of MIS12 ensures accurate kinetochore-microtubule attachment by expanding the fibrous corona.

Abstract

Genomic integrity in mammalian cells relies on faithful chromosome segregation. Kinetochores capture microtubules and establish robust kinetochore-microtubule attachment to achieve accurate segregation. The MIS12 complex, a tetramer comprising MIS12, DSN1, NSL1, and PMF1, plays a critical role in kinetochore-microtubule attachment. However, how the MIS12 complex functions at the kinetochore-microtubule interface is not fully understood. Here, we found that MIS12 is phosphorylated at Ser177 by NEK2A from prophase to prometaphase. Phosphorylation of MIS12 expands the projection of the outer kinetochore, known as the fibrous corona, thus facilitating the attachment of kinetochores to microtubules. When chromosomes align at the equatorial plate, Ser177 on MIS12 is dephosphorylated by PP1, which is required for kinetochore compaction and end-on attachment conversion. We uncovered that the dynamic phosphorylation of MIS12 regulates the expansion-compaction transition of the outermost layer of kinetochores, ensuring accurate kinetochore-microtubule attachment and faithful chromosome segregation.