title: Aluminum-induced kinesin inactivation as potential molecular cause of impairment of neuronal transport processes.
abstract: It is commonly accepted that aluminum ions may initiate the development of diverse diseases, including neurological disorders. So far, our knowledge of the molecular mechanisms of the interaction of aluminum with defined cellular structures has been still fragmentary. As functional key tasks of neuronal cells essentially depend on the activity of kinesin, we wanted to find out whether this motor protein represents a molecular target for aluminum. We demonstrate that aluminum ions inhibit (IC50 ∼50 μM) the ATPase of the neuron-specific kinesin KIF5A. The ATPase-active center itself, which is located in the kinesin motor domain, does not seem to be directly affected by aluminum. Our results suggest that inhibition is preferentially caused by aluminum binding to some sequence within the kinesin stalk leading to a conformational state of the kinesin molecule, similar to those described in cases of kinesin autoinhibition caused by motor domain-tail binding. Because of the relative high sequence conservation of mammalian kinesin-1 (to which KIF5A belongs), we assume that also in non-neuronal cells the intracellular transport can be affected by aluminum ions.
authors: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Beutenbergstraße 11, D-07745 Jena, Germany.
authors: Konrad J
authors: KJ
authors: Böhm
authors: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Beutenbergstraße 11, D-07745 Jena, Germany.
authors: Mitra
authors: M
authors: Shabanpour
authors: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Beutenbergstraße 11, D-07745 Jena, Germany.
authors: Nikolina
authors: N
authors: Kalchishkova
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: C500506:KIF5A protein, human; D000535:Aluminum; D016547:Kinesins