title: Effects of wild type tau and disease-linked tau mutations on microtubule organization and intracellular trafficking.
abstract: We investigate the effects of transient expression of wild type (WT) and disease-linked mutations of tau (R406W, P301L, ΔN296) on cytoskeletal organization and cargo transport in COS-7 cells, which are natively tau-free. The introduction of tau proteins (either WT or mutant forms) leads to a dramatic restructuring of the microtubule cytoskeleton, as observed using immunofluorescence microscopy. Yet, this microtubule bundling and aggregation has a modest effect on the speed and travel distance of motor-driven cargo transport, as measured by the motions of fluorescently-labeled lysosomes. This suggests that localized transport events are insensitive to the global structure of the microtubule cytoskeleton. Importantly, we also found no evidence that the disease-linked tau mutants were particularly toxic; in fact we found that expression of mutant and WT tau had similar effects on overall microtubule structure and transport phenotypes.
authors.affiliation: Department of Materials, University of California, Santa Barbara, Santa Barbara, CA, USA; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, USA.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Yu
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, USA; Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Feinstein
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, USA; Department of Mechanical Engineering, University of California, Santa Barbara, Santa Barbara, CA, USA. Electronic address: valentine@engineering.ucsb.edu.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Valentine
mesh_terms: D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002522:Chlorocebus aethiops; D008870:Microtubules / Q000502:physiology*; D009154:Mutation; D016875:tau Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D016875:tau Proteins
keywords: Intracellular transport; Microtubules; Tau