SUMMARY Kinetochores couple chromosomes to the assembling and disassembling tips of microtubules, a dynamic behavior that is fundamental to mitosis in all eukaryotes but poorly understood. Genetic, biochemical and structural studies implicate the Ndc80 complex as a direct point of contact between kinetochores and microtubules, but these approaches provide only a static view. Here, using techniques for manipulating and tracking individual molecules in vitro, we demonstrate that the Ndc80 complex is capable of forming the dynamic, load-bearing attachments to assembling and disassembling tips required for coupling in vivo. We also establish that Ndc80-based coupling likely occurs through a biased diffusion mechanism, and that this activity is conserved from yeast to humans. Our findings demonstrate how an ensemble of Ndc80 complexes may provide a ‘slip clutch’ that allows the kinetochore to maintain a load-bearing tip attachment during both microtubule assembly and disassembly.

The Dam1 complex, regulated by aurora B phosphorylation, confers a more stable microtubule association for the Ndc80 complex at kinetochores (see also related paper by Lampert et al. in this issue).

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The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells1. We have functionally dissected the structural features responsible for MCAK’s potent microtubule depolymerization activity. MCAK’s positively charged neck enhances its delivery to microtubule ends, not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK’s ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK’s ability to remove tubulin subunits. The reported kinetics for these events predict a non-specific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule binding proteins.