Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress

The Journal of Cell Biology
K StamerE-M Mandelkow

Abstract

We studied the effect of microtubule-associated tau protein on trafficking of vesicles and organelles in primary cortical neurons, retinal ganglion cells, and neuroblastoma cells. Tau inhibits kinesin-dependent transport of peroxisomes, neurofilaments, and Golgi-derived vesicles into neurites. Loss of peroxisomes makes cells vulnerable to oxidative stress and leads to degeneration. In particular, tau inhibits transport of amyloid precursor protein (APP) into axons and dendrites, causing its accumulation in the cell body. APP tagged with yellow fluorescent protein and transfected by adenovirus associates with vesicles moving rapidly forward in the axon (approximately 80%) and slowly back (approximately 20%). Both movements are strongly inhibited by cotransfection with fluorescently tagged tau (cyan fluorescent protein-tau) as seen by two-color confocal microscopy. The data suggests a linkage between tau and APP trafficking, which may be significant in Alzheimer's disease.

References

Oct 25, 1977·Journal of Molecular Biology·D W ClevelandM W Kirschner
Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Dec 1, 1986·The Journal of Cell Biology·D G Drubin, M W Kirschner
Oct 1, 1985·The Journal of Cell Biology·L I BinderL I Rebhun
Jan 1, 1995·Methods in Cell Biology·M P MattsonR J Mark
Jan 1, 1994·Brain Research Bulletin·B M Riederer, L I Binder
Dec 1, 1995·The Journal of Cell Biology·R L Morris, P J Hollenbeck
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·H XuS Gandy
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Mar 4, 1998·Current Opinion in Cell Biology·N HirokawaY Okada
Aug 13, 1998·Journal of Neural Transmission. Supplementum·R D Terry
Aug 15, 1998·The Journal of Biological Chemistry·H LiaoG G Gundersen
Aug 26, 1998·Biochimica Et Biophysica Acta·F Bradke, C G Dotti
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P GreenfieldH Xu
Feb 27, 1999·Current Opinion in Cell Biology·G G Gundersen, T A Cook
Mar 24, 1999·Trends in Cell Biology·J EllenbergJ F Presley
Feb 19, 2000·Current Opinion in Cell Biology·S L Rogers, V I Gelfand
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·P J MuchowskiF U Hartl
Sep 1, 2000·Brain Research. Brain Research Reviews·L BuéeP R Hof
Dec 21, 2000·Trends in Cell Biology·R R Kopito
Feb 13, 2001·Current Opinion in Cell Biology·M L Garcia, D W Cleveland
Feb 13, 2001·Current Opinion in Cell Biology·Y H ChouR D Goldman
Mar 10, 2001·The Journal of Cell Biology·K J VerheyB Margolis
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·L S Goldstein

❮ Previous
Next ❯

Citations

Jan 11, 2005·Neurotoxicity Research·Tomás PalomoRichard M Kostrzewa
Sep 6, 2007·Acta Neuropathologica·Stephan FrankMarkus Tolnay
Dec 21, 2010·Acta Neuropathologica·Heiko Braak, Kelly Del Tredici
Apr 26, 2011·Acta Neuropathologica·Heiko Braak, Kelly Del Tredici
May 20, 2011·Acta Neuropathologica·Jianqiu KouJohannes Berger
Mar 7, 2012·Cell and Tissue Research·Paul LingorMathias Bähr
Jun 1, 2006·Journal of Neural Transmission·G NiewiadomskaG Riedel
Feb 8, 2007·Journal of Plant Research·Takahiro Hamada
Jun 21, 2008·Neuromolecular Medicine·P Hemachandra Reddy
Jul 19, 2008·Journal of Molecular Neuroscience : MN·Tal Shprung, Illana Gozes
Mar 11, 2010·Molecular Neurobiology·Anne EckertJürgen Götz
Mar 27, 2013·Ageing Research Reviews·Johanna L CriminsTara L Spires-Jones
Dec 31, 2003·Molecular and Cellular Neurosciences·Christian BarbatoClaudio Passananti
Apr 13, 2005·Trends in Molecular Medicine·Hyoung-Gon LeeMark A Smith
Apr 2, 2004·Neurobiology of Disease·Susanna Schraen-MaschkeBernard Sablonnière
Dec 4, 2003·Neurobiology of Aging·E-M MandelkowE Mandelkow
Dec 4, 2003·Neurobiology of Aging·Stephen W Scheff, Douglas A Price
Oct 1, 2013·Neuropharmacology·Amy M PoolerDiane P Hanger
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anja Schneider, Eckhard Mandelkow
Apr 9, 2005·Trends in Cell Biology·Peter W Baas, Liang Qiang
Nov 26, 2003·Experimental Neurology·Andrew GroverMichael Hutton
Nov 14, 2002·Neurotoxicology·Lisa Skipper, Matt Farrer
Jan 22, 2003·Trends in Neurosciences·Ahmad SalehiWilliam C Mobley
Sep 11, 2002·Trends in Neurosciences·Michael P Coleman, V Hugh Perry
Feb 22, 2003·Biochimie·Janice RobertsonJean-Pierre Julien
Dec 24, 2002·Trends in Cell Biology·Eckhard Mandelkow, Eva-Maria Mandelkow
Aug 7, 2003·Neurobiology of Disease·Ben Roediger, Patricia J Armati
Jun 5, 2012·Nano Letters·Claudia SchmidtViola Vogel
Feb 9, 2012·Nature Medicine·Jeannette N StankowskiTed M Dawson
Sep 16, 2004·Nature Reviews. Molecular Cell Biology·Lynne Chang, Robert D Goldman
Oct 24, 2009·Nature Reviews. Molecular Cell Biology·Kristen J Verhey, Jennetta W Hammond
Nov 8, 2002·Journal of Neurochemistry·William H StoothoffGail V W Johnson
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lars M IttnerJürgen Götz
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Robert A RissmanPaul E Sawchenko

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Methods Mentioned

BETA
transfection
light microscopy
confocal microscopy
protein folding
FCS
PCR
fluorescence microscopy
gel filtration
confocal

Software Mentioned

MetaMorph

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