Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling

Errorless chromosome segregation requires load-bearing attachments of the plus ends of spindle microtubules to chromosome structures named kinetochores. How these end-on kinetochore attachments are established following initial lateral contacts with the microtubule lattice is poorly understood. Two microtubule-binding complexes, the Ndc80 and Ska complexes, are important for efficient end-on coupling and may function as a unit in this process, but precise conditions for their interaction are unknown. Here, we report that the Ska-Ndc80 interaction is phosphorylation-dependent and does not require microtubules, applied force, or several previously identified functional determinants including the Ndc80-loop and the Ndc80-tail. Under force, Ska stabilizes end-on microtubule attachments in parallel with the Ndc80-tail, which we reveal to be essential for end-tracking by Ndc80 multimers. Modulation of force-coupling efficiency demonstrates that the duration of stalled microtubule disassembly predicts whether a microtubule is stabilized and rescued by the kinetochore, likely reflecting a structural transition of the microtubule end.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC=\"FIGDIR/small/675363v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (38K):\norg.highwire.dtl.DTLVardef@9e6207org.highwire.dtl.DTLVardef@35f668org.highwire.dtl.DTLVardef@c43242org.highwire.dtl.DTLVardef@bfcc13_HPS_FORMAT_FIGEXP M_FIG C_FIG