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Prion protein impairs kinesin-driven 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. Our previous studies...
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Published in: | Biochemical and biophysical research communications 2012-09, Vol.425 (4), p.788-793 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | ► 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.
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. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2012.07.153 |