MCAK/Kif2C Centromeric Activity Level Tunes K-fiber Stability

Overview

Journal bioRxiv

Date 2025 Mar 3

PMID 40027728

Authors

Linda Wordeman

Mike Wagenbach

Juan Jesus Vicente

Affiliations

Soon will be listed here.

Abstract

MCAK/Kif2C is a microtubule-depolymerizing kinesin that is implicated in the correction of chromosome attachment errors. When this protein is eliminated from kinetochores, cells exhibit delayed congression and a modest increase in chromosome mis-segregation. Curiously, MCAK/Kif2C overexpression (OE) promotes these same defects. These mitotic delays are restricted to prometaphase and can be rescued by modulating MCAK/Kif2C activity solely at the centromere. Both excessive depletion and surplus levels of centromeric MCAK/Kif2C increased inter-kinetochore distances (IKDs) commensurate with an increase in acetylated tubulin in the spindle, a readout for k-fiber stability. Because both high and low levels of centromere-associated MCAK/Kif2C increased k-fiber stability, we conclude that this is the likely mechanism for the increased chromosome segregation errors observed in both these antagonistic conditions. Loss of centromeric MCAK/Kif2C delayed the conversion from lateral to end-on motility was delayed in MCAK/Kif2C-depleted cells. This likely represents the key activity that MCAK/Kif2C imparts to the centromere which, when present at consistently incorrect levels, slows k-fiber turnover and congression.

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