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

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Genomic integrity in mammalian cells depends on accurate chromosome segregation.
• Kinetochores are crucial for capturing microtubules and ensuring proper chromosome movement.
• The MIS12 complex is essential for kinetochore-microtubule attachment, but its precise function remains unclear.

Purpose of the Study:

• To investigate the role of MIS12 complex regulation in kinetochore-microtubule attachment.
• To elucidate the mechanism by which MIS12 complex ensures faithful chromosome segregation.

Main Methods:

• Investigated the phosphorylation status of MIS12 at Ser177.
• Utilized cell-based assays to observe the effects of MIS12 phosphorylation on kinetochore structure and microtubule attachment.
• Examined the roles of NEK2A and PP1 in regulating MIS12 phosphorylation dynamics.

Main Results:

• MIS12 is phosphorylated by NEK2A at Ser177 during prophase to prometaphase.
• Phosphorylation of MIS12 leads to the expansion of the fibrous corona, enhancing kinetochore-microtubule attachment.
• Dephosphorylation of MIS12 by PP1 at the equatorial plate is necessary for kinetochore compaction and end-on attachment.

Conclusions:

• Dynamic phosphorylation of MIS12 governs the transition between fibrous corona expansion and kinetochore compaction.
• This phosphorylation-dependent regulation is critical for robust kinetochore-microtubule attachment and accurate chromosome segregation.
• The study reveals a novel regulatory mechanism for maintaining genomic stability during cell division.