title: Prion protein impairs kinesin-driven transport.
abstract: 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.
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Nieznanska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Dudek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zajkowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Szczesna
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Kasprzak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Nieznanski
mesh_terms: D000818:Animals; D002455:Cell Division; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D016716:PC12 Cells; D011328:Prions / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D011328:Prions; D014404:Tubulin; D016547:Kinesins