Prion protein impairs kinesin-driven transport

Our previous studies have demonstrated that prion protein (PrP) leads to disassembly of microtubular cytoskeleton through binding to tubulin and its oligomerization. Here we found that PrP-treated cells exhibited improper morphology of mitotic spindles. Formation of aberrant spindles may result not only from altered microtubule dynamics – as expected from PrP-induced tubulin oligomerization – but also from impairing the function of molecular motors. Therefore we checked whether binding of PrP to microtubules affected movement generated by Ncd – a kinesin responsible for the proper organization of division spindles. We found that PrP inhibited Ncd-driven transport of microtubules. Most probably, the inhibition of the microtubule movement resulted from PrP-induced changes in the microtubule structure since Ncd-microtubule binding was reduced already at low PrP to tubulin molar ratios. This study suggests another plausible mechanism of PrP cytotoxicity related to the interaction with tubulin, namely impeding microtubule-dependent transport.

► Prion protein (PrP) affects mitotic spindles of cultured cells. ► PrP inhibits kinesin-driven transport of microtubules in motility assay. ► PrP reduces kinesin-microtubule binding. ► Affected axonal transport in prion diseases may result from impaired by PrP kinesin function.