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

doi:10.1083/jcb.200108057

Published 18 March 2002. doi:10.1083/jcb.200108057

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© The Rockefeller University Press, 0021-9525/2002/3/1051 $5.00
The Journal of Cell Biology, Volume 156, Number 6, March 18, 2002 1051-1063

Article

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

K. Stamer, R. Vogel, E. Thies, E. Mandelkow and E.-M. Mandelkow

Max-Planck-Unit for Structural Molecular Biology, 22607 Hamburg, Germany

Address correspondence to Dr. Eva-Maria Mandelkow, Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany. Tel.: 49-40-8998-2810. Fax: 49-40-8971-6822. E-mail: mand{at}mpasmb.desy.de

We studied the effect of microtubule-associated tau proteinon trafficking of vesicles and organelles in primary corticalneurons, retinal ganglion cells, and neuroblastoma cells. Tauinhibits kinesin-dependent transport of peroxisomes, neurofilaments,and Golgi-derived vesicles into neurites. Loss of peroxisomesmakes 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 inthe cell body. APP tagged with yellow fluorescent protein andtransfected by adenovirus associates with vesicles moving rapidlyforward in the axon ( $~$ 80%) and slowly back ( $~$ 20%). Both movementsare strongly inhibited by cotransfection with fluorescentlytagged tau (cyan fluorescent protein–tau) as seen by two-colorconfocal microscopy. The data suggests a linkage between tauand APP trafficking, which may be significant in Alzheimer'sdisease.

Key Words: axonal traffic; microtubules; tau protein; amyloid precursor protein; oxidative stress

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Liazoghli, D., Perreault, S., Micheva, K. D., Desjardins, M., Leclerc, N. (2005). Fragmentation of the Golgi Apparatus Induced by the Overexpression of Wild-Type and Mutant Human Tau Forms in Neurons. Am. J. Pathol. 166: 1499-1514 [Abstract] [Full Text]
Darios, F., Muriel, M.-P., Khondiker, M. E., Brice, A., Ruberg, M. (2005). Neurotoxic Calcium Transfer from Endoplasmic Reticulum to Mitochondria Is Regulated by Cyclin-Dependent Kinase 5-Dependent Phosphorylation of Tau. J. Neurosci. 25: 4159-4168 [Abstract] [Full Text]
Levy, S. F., LeBoeuf, A. C., Massie, M. R., Jordan, M. A., Wilson, L., Feinstein, S. C. (2005). Three- and Four-repeat Tau Regulate the Dynamic Instability of Two Distinct Microtubule Subpopulations in Qualitatively Different Manners: IMPLICATIONS FOR NEURODEGENERATION. J. Biol. Chem. 280: 13520-13528 [Abstract] [Full Text]
Berliocchi, L., Fava, E., Leist, M., Horvat, V., Dinsdale, D., Read, D., Nicotera, P. (2005). Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis. JCB 168: 607-618 [Abstract] [Full Text]
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Samsonov, A., Yu, J.-Z., Rasenick, M., Popov, S. V. (2004). Tau interaction with microtubules in vivo. J. Cell Sci. 117: 6129-6141 [Abstract] [Full Text]
Johnson, G. V. W., Stoothoff, W. H. (2004). Tau phosphorylation in neuronal cell function and dysfunction. J. Cell Sci. 117: 5721-5729 [Abstract] [Full Text]
Lee, H.-g., Moreira, P. I., Zhu, X., Smith, M. A., Perry, G. (2004). Staying Connected: Synapses in Alzheimer Disease. Am. J. Pathol. 165: 1461-1464 [Full Text]
Mandelkow, E.-M., Thies, E., Trinczek, B., Biernat, J., Mandelkow, E. (2004). MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. JCB 167: 99-110 [Abstract] [Full Text]
Chan, W. K.-H., Dickerson, A., Ortiz, D., Pimenta, A. F., Moran, C. M., Motil, J., Snyder, S. J., Malik, K., Pant, H. C., Shea, T. B. (2004). Mitogen-activated protein kinase regulates neurofilament axonal transport. J. Cell Sci. 117: 4629-4642 [Abstract] [Full Text]
Bunker, J. M., Wilson, L., Jordan, M. A., Feinstein, S. C. (2004). Modulation of Microtubule Dynamics by Tau in Living Cells: Implications for Development and Neurodegeneration. Mol. Biol. Cell 15: 2720-2728 [Abstract] [Full Text]
Zhang, B., Higuchi, M., Yoshiyama, Y., Ishihara, T., Forman, M. S., Martinez, D., Joyce, S., Trojanowski, J. Q., Lee, V. M.-Y. (2004). Retarded Axonal Transport of R406W Mutant Tau in Transgenic Mice with a Neurodegenerative Tauopathy. J. Neurosci. 24: 4657-4667 [Abstract] [Full Text]
Shea, T. B., Yabe, J. T., Ortiz, D., Pimenta, A., Loomis, P., Goldman, R. D., Amin, N., Pant, H. C. (2004). Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons. J. Cell Sci. 117: 933-941 [Abstract] [Full Text]
Helfand, B. T., Chang, L., Goldman, R. D. (2004). Intermediate filaments are dynamic and motile elements of cellular architecture. J. Cell Sci. 117: 133-141 [Abstract] [Full Text]
Klein, R. L., Lin, W.-L., Dickson, D. W., Lewis, J., Hutton, M., Duff, K., Meyer, E. M., King, M. A. (2004). Rapid Neurofibrillary Tangle Formation after Localized Gene Transfer of Mutated Tau. Am. J. Pathol. 164: 347-353 [Abstract] [Full Text]
Yoshiyama, Y., Zhang, B., Bruce, J., Trojanowski, J. Q., Lee, V. M.-Y. (2003). Reduction of Detyrosinated Microtubules and Golgi Fragmentation Are Linked to Tau-Induced Degeneration in Astrocytes. J. Neurosci. 23: 10662-10671 [Abstract] [Full Text]
Kraemer, B. C., Zhang, B., Leverenz, J. B., Thomas, J. H., Trojanowski, J. Q., Schellenberg, G. D. (2003). From the Cover: Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc. Natl. Acad. Sci. USA 100: 9980-9985 [Abstract] [Full Text]
Panda, D., Samuel, J. C., Massie, M., Feinstein, S. C., Wilson, L. (2003). Differential regulation of microtubule dynamics by three- and four-repeat tau: Implications for the onset of neurodegenerative disease. Proc. Natl. Acad. Sci. USA 100: 9548-9553 [Abstract] [Full Text]
Lilla, V., Webb, G., Rickenbach, K., Maturana, A., Steiner, D. F., Halban, P. A., Irminger, J.-C. (2003). Differential Gene Expression in Well-Regulated and Dysregulated Pancreatic {beta}-Cell (MIN6) Sublines. Endocrinology 144: 1368-1379 [Abstract] [Full Text]
Brownlees, J., Ackerley, S., Grierson, A. J., Jacobsen, N. J.O., Shea, K., Anderton, B. H., Leigh, P. N., Shaw, C. E., Miller, C. C.J. (2002). Charcot-Marie-Tooth disease neurofilament mutations disrupt neurofilament assembly and axonal transport. Hum Mol Genet 11: 2837-2844 [Abstract] [Full Text]
Biernat, J., Wu, Y.-Z., Timm, T., Zheng-Fischhofer, Q., Mandelkow, E., Meijer, L., Mandelkow, E.-M. (2002). Protein Kinase MARK/PAR-1 Is Required for Neurite Outgrowth and Establishment of Neuronal Polarity. Mol. Biol. Cell 13: 4013-4028 [Abstract] [Full Text]
Khaled, M., Larribere, L., Bille, K., Aberdam, E., Ortonne, J.-P., Ballotti, R., Bertolotto, C. (2002). Glycogen Synthase Kinase 3beta Is Activated by cAMP and Plays an Active Role in the Regulation of Melanogenesis. J. Biol. Chem. 277: 33690-33697 [Abstract] [Full Text]
Utton, M. A., Connell, J., Asuni, A. A., van Slegtenhorst, M., Hutton, M., de Silva, R., Lees, A. J., Miller, C. C. J., Anderton, B. H. (2002). The Slow Axonal Transport of the Microtubule-Associated Protein Tau and the Transport Rates of Different Isoforms and Mutants in Cultured Neurons. J. Neurosci. 22: 6394-6400 [Abstract] [Full Text]