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bioRxiv · 10.1101/2025.02.16.638494

MCAK/Kif2C centromeric activity level tunes K-fiber stability.

Wordeman, L.·Wagenbach, M.·Vicente, J. J.
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Abstract

MCAK/Kif2C is a microtubule-depolymerizing kinesin implicated in the correction of chromosome attachment errors. When eliminated from kinetochores, cells exhibit delayed congression and a modest increase in chromosome missegregation. Curiously, MCAK/Kif2C overexpression (OE) promotes these same defects. Both depletion and excess levels of centromeric MCAK/Kif2C increase acetylated tubulin levels in the spindle, suggesting an increase in k-fiber stability. We conclude that this is the likely mechanism for the increase in chromosome segregation errors observed in both of these antagonistic conditions. Reduced MCAK/Kif2C increased the tubulin ratio on the two faces of the kinetochore, suggesting a greater likelihood of erroneous lateral MT interactions. In contrast, excess MCAK/Kif2C reduced the tubulin ratio at the kinetochore, stabilizing end-on MT interactions that increase the IKD and ultimately culminate in excessive stabilization of K-fiber microtubules. Both of these conditions promote chromosome segregation errors. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/638494v2_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@108570org.highwire.dtl.DTLVardef@a891a3org.highwire.dtl.DTLVardef@f1761borg.highwire.dtl.DTLVardef@811c70_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefCell biology; Chromosome organization HighlightsO_LIAn optimal level of MCAK/Kif2C ensures error-correction during mitosis C_LIO_LIBoth excess or insufficient MCAK/Kif2C suppresses MT turnover in k-fibers C_LIO_LIExcess MCAK/Kif2C deforms kinetochores with uncoordinated movement C_LIO_LIInsufficient MCAK/Kif2C deforms kinetochores with unresolved lateral MTs C_LI

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Wordeman, L., Wagenbach, M., Vicente, J. J.. 2025-02-17. MCAK/Kif2C centromeric activity level tunes K-fiber stability.. https://doi.org/10.1101/2025.02.16.638494

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