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

This Article

	Full Text
	Full Text (PDF, 580K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Stamer, K.
	Articles by Mandelkow, E.-M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Stamer, K.
	Articles by Mandelkow, E.-M.


Related Collections

	Related Article

Social Bookmarking

	What's this?

© 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

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

Related Article

Finding the dark side of tau: Alan W. Dove
J. Cell Biol. 2002 156: 938. [Full Text] [PDF]

This article has been cited by other articles:

Ma, H., Cai, Q., Lu, W., Sheng, Z.-H., Mochida, S. (2009). KIF5B Motor Adaptor Syntabulin Maintains Synaptic Transmission in Sympathetic Neurons. J. Neurosci. 29: 13019-13029 [Abstract] [Full Text]
Perrot, R., Julien, J.-P. (2009). Real-time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments. FASEB J. 23: 3213-3225 [Abstract] [Full Text]
Reiner, O., Shmueli, A., Sapir, T. (2009). Neuronal Migration and Neurodegeneration: 2 Sides of the Same Coin. Cereb Cortex 19: i42-i48 [Abstract] [Full Text]
Matsuda, S., Matsuda, Y., D'Adamio, L. (2009). BRI3 Inhibits Amyloid Precursor Protein Processing in a Mechanistically Distinct Manner from Its Homologue Dementia Gene BRI2. J. Biol. Chem. 284: 15815-15825 [Abstract] [Full Text]
Falzone, T. L., Stokin, G. B., Lillo, C., Rodrigues, E. M., Westerman, E. L., Williams, D. S., Goldstein, L. S. B. (2009). Axonal Stress Kinase Activation and Tau Misbehavior Induced by Kinesin-1 Transport Defects. J. Neurosci. 29: 5758-5767 [Abstract] [Full Text]
Hoozemans, J. J.M., van Haastert, E. S., Nijholt, D. A.T., Rozemuller, A. J.M., Eikelenboom, P., Scheper, W. (2009). The Unfolded Protein Response Is Activated in Pretangle Neurons in Alzheimer's Disease Hippocampus. Am. J. Pathol. 174: 1241-1251 [Abstract] [Full Text]
Muresan, V., Varvel, N. H., Lamb, B. T., Muresan, Z. (2009). The Cleavage Products of Amyloid-{beta} Precursor Protein Are Sorted to Distinct Carrier Vesicles That Are Independently Transported within Neurites. J. Neurosci. 29: 3565-3578 [Abstract] [Full Text]
LeBoeuf, A. C., Levy, S. F., Gaylord, M., Bhattacharya, A., Singh, A. K., Jordan, M. A., Wilson, L., Feinstein, S. C. (2008). FTDP-17 Mutations in Tau Alter the Regulation of Microtubule Dynamics: AN "ALTERNATIVE CORE" MODEL FOR NORMAL AND PATHOLOGICAL TAU ACTION. J. Biol. Chem. 283: 36406-36415 [Abstract] [Full Text]
Ittner, L. M., Fath, T., Ke, Y. D., Bi, M., van Eersel, J., Li, K. M., Gunning, P., Gotz, J. (2008). Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia. Proc. Natl. Acad. Sci. USA 105: 15997-16002 [Abstract] [Full Text]
Cuchillo-Ibanez, I., Seereeram, A., Byers, H. L., Leung, K.-Y., Ward, M. A., Anderton, B. H., Hanger, D. P. (2008). Phosphorylation of tau regulates its axonal transport by controlling its binding to kinesin. FASEB J. 22: 3186-3195 [Abstract] [Full Text]
Tobin, J. E., Latourelle, J. C., Lew, M. F., Klein, C., Suchowersky, O., Shill, H. A., Golbe, L. I., Mark, M. H., Growdon, J. H., Wooten, G. F., Racette, B. A., Perlmutter, J. S., Watts, R., Guttman, M., Baker, K. B., Goldwurm, S., Pezzoli, G., Singer, C., Saint-Hilaire, M. H., Hendricks, A. E., Williamson, S., Nagle, M. W., Wilk, J. B., Massood, T., Laramie, J. M., DeStefano, A. L., Litvan, I., Nicholson, G., Corbett, A., Isaacson, S., Burn, D. J., Chinnery, P. F., Pramstaller, P. P., Sherman, S., Al-hinti, J., Drasby, E., Nance, M., Moller, A. T., Ostergaard, K., Roxburgh, R., Snow, B., Slevin, J. T., Cambi, F., Gusella, J. F., Myers, R. H. (2008). Haplotypes and gene expression implicate the MAPT region for Parkinson disease: The GenePD Study. Neurology 71: 28-34 [Abstract] [Full Text]
Terwel, D., Muyllaert, D., Dewachter, I., Borghgraef, P., Croes, S., Devijver, H., Van Leuven, F. (2008). Amyloid Activates GSK-3{beta} to Aggravate Neuronal Tauopathy in Bigenic Mice. Am. J. Pathol. 172: 786-798 [Abstract] [Full Text]
Yuan, A., Kumar, A., Peterhoff, C., Duff, K., Nixon, R. A. (2008). Axonal Transport Rates In Vivo Are Unaffected by Tau Deletion or Overexpression in Mice. J. Neurosci. 28: 1682-1687 [Abstract] [Full Text]
Lyons, D. A., Naylor, S. G., Mercurio, S., Dominguez, C., Talbot, W. S. (2008). KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome. Development 135: 599-608 [Abstract] [Full Text]
Mocanu, M.-M., Nissen, A., Eckermann, K., Khlistunova, I., Biernat, J., Drexler, D., Petrova, O., Schonig, K., Bujard, H., Mandelkow, E., Zhou, L., Rune, G., Mandelkow, E.-M. (2008). The Potential for -Structure in the Repeat Domain of Tau Protein Determines Aggregation, Synaptic Decay, Neuronal Loss, and Coassembly with Endogenous Tau in Inducible Mouse Models of Tauopathy. J. Neurosci. 28: 737-748 [Abstract] [Full Text]
Elliott, E., Tsvetkov, P., Ginzburg, I. (2007). BAG-1 Associates with Hsc70{middle dot}Tau Complex and Regulates the Proteasomal Degradation of Tau Protein. J. Biol. Chem. 282: 37276-37284 [Abstract] [Full Text]
De Vos, K. J., Chapman, A. L., Tennant, M. E., Manser, C., Tudor, E. L., Lau, K.-F., Brownlees, J., Ackerley, S., Shaw, P. J., McLoughlin, D. M., Shaw, C. E., Leigh, P. N., Miller, C. C.J., Grierson, A. J. (2007). Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 16: 2720-2728 [Abstract] [Full Text]
Eckermann, K., Mocanu, M.-M., Khlistunova, I., Biernat, J., Nissen, A., Hofmann, A., Schonig, K., Bujard, H., Haemisch, A., Mandelkow, E., Zhou, L., Rune, G., Mandelkow, E.-M. (2007). The beta-Propensity of Tau Determines Aggregation and Synaptic Loss in Inducible Mouse Models of Tauopathy. J. Biol. Chem. 282: 31755-31765 [Abstract] [Full Text]
Konzack, S., Thies, E., Marx, A., Mandelkow, E.-M., Mandelkow, E. (2007). Swimming against the Tide: Mobility of the Microtubule-Associated Protein Tau in Neurons. J. Neurosci. 27: 9916-9927 [Abstract] [Full Text]
Dawson, H. N., Cantillana, V., Chen, L., Vitek, M. P. (2007). The Tau N279K Exon 10 Splicing Mutation Recapitulates Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17 Tauopathy in a Mouse Model. J. Neurosci. 27: 9155-9168 [Abstract] [Full Text]
Kraemer, B. C., Schellenberg, G. D. (2007). SUT-1 enables tau-induced neurotoxicity in C. elegans. Hum Mol Genet 16: 1959-1971 [Abstract] [Full Text]
Chun, W., Johnson, G. V. W. (2007). Activation of Glycogen Synthase Kinase 3beta Promotes the Intermolecular Association of Tau: THE USE OF FLUORESCENCE RESONANCE ENERGY TRANSFER MICROSCOPY. J. Biol. Chem. 282: 23410-23417 [Abstract] [Full Text]
Escobar-Khondiker, M., Hollerhage, M., Muriel, M.-P., Champy, P., Bach, A., Depienne, C., Respondek, G., Yamada, E. S., Lannuzel, A., Yagi, T., Hirsch, E. C., Oertel, W. H., Jacob, R., Michel, P. P., Ruberg, M., Hoglinger, G. U. (2007). Annonacin, a Natural Mitochondrial Complex I Inhibitor, Causes Tau Pathology in Cultured Neurons. J. Neurosci. 27: 7827-7837 [Abstract] [Full Text]
Mus, E., Hof, P. R., Tiedge, H. (2007). Dendritic BC200 RNA in aging and in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 104: 10679-10684 [Abstract] [Full Text]
Rissman, R. A., Lee, K.-F., Vale, W., Sawchenko, P. E. (2007). Corticotropin-Releasing Factor Receptors Differentially Regulate Stress-Induced Tau Phosphorylation. J. Neurosci. 27: 6552-6562 [Abstract] [Full Text]
Goldsbury, C., Thies, E., Konzack, S., Mandelkow, E.-M. (2007). Quantification of Amyloid Precursor Protein and Tau for the Study of Axonal Traffic Pathways. J. Neurosci. 27: 3357-3363 [Full Text]
Thies, E., Mandelkow, E.-M. (2007). Missorting of Tau in Neurons Causes Degeneration of Synapses That Can Be Rescued by the Kinase MARK2/Par-1. J. Neurosci. 27: 2896-2907 [Abstract] [Full Text]
Satpute-Krishnan, P., DeGiorgis, J. A., Conley, M. P., Jang, M., Bearer, E. L. (2006). A peptide zipcode sufficient for anterograde transport within amyloid precursor protein. Proc. Natl. Acad. Sci. USA 103: 16532-16537 [Abstract] [Full Text]
Ashby, J., Boutant, E., Seemanpillai, M., Sambade, A., Ritzenthaler, C., Heinlein, M. (2006). Tobacco mosaic virus movement protein functions as a structural microtubule-associated protein.. J. Virol. 80: 8329-8344 [Abstract] [Full Text]
Plattner, F., Angelo, M., Giese, K. P. (2006). The Roles of Cyclin-dependent Kinase 5 and Glycogen Synthase Kinase 3 in Tau Hyperphosphorylation. J. Biol. Chem. 281: 25457-25465 [Abstract] [Full Text]
Kraemer, B. C., Burgess, J. K., Chen, J. H., Thomas, J. H., Schellenberg, G. D. (2006). Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans. Hum Mol Genet 15: 1483-1496 [Abstract] [Full Text]
Nguyen, T., Bjorkman, J., Paton, B. C., Crane, D. I. (2006). Failure of microtubule-mediated peroxisome division and trafficking in disorders with reduced peroxisome abundance. J. Cell Sci. 119: 636-645 [Abstract] [Full Text]
McGuire, J. R., Rong, J., Li, S.-H., Li, X.-J. (2006). Interaction of Huntingtin-associated Protein-1 with Kinesin Light Chain: IMPLICATIONS IN INTRACELLULAR TRAFFICKING IN NEURONS. J. Biol. Chem. 281: 3552-3559 [Abstract] [Full Text]
Khlistunova, I., Biernat, J., Wang, Y., Pickhardt, M., von Bergen, M., Gazova, Z., Mandelkow, E., Mandelkow, E.-M. (2006). Inducible Expression of Tau Repeat Domain in Cell Models of Tauopathy: AGGREGATION IS TOXIC TO CELLS BUT CAN BE REVERSED BY INHIBITOR DRUGS. J. Biol. Chem. 281: 1205-1214 [Abstract] [Full Text]
Santos, M. J., Quintanilla, R. A., Toro, A., Grandy, R., Dinamarca, M. C., Godoy, J. A., Inestrosa, N. C. (2005). Peroxisomal Proliferation Protects from {beta}-Amyloid Neurodegeneration. J. Biol. Chem. 280: 41057-41068 [Abstract] [Full Text]
Muresan, Z., Muresan, V. (2005). Coordinated transport of phosphorylated amyloid-{beta} precursor protein and c-Jun NH2-terminal kinase-interacting protein-1. JCB 171: 615-625 [Abstract] [Full Text]
Utton, M. A., Noble, W. J., Hill, J. E., Anderton, B. H., Hanger, D. P. (2005). Molecular motors implicated in the axonal transport of tau and {alpha}-synuclein. J. Cell Sci. 118: 4645-4654 [Abstract] [Full Text]
Higuchi, M., Zhang, B., Forman, M. S., Yoshiyama, Y., Trojanowski, J. Q., Lee, V. M.-Y. (2005). Axonal Degeneration Induced by Targeted Expression of Mutant Human Tau in Oligodendrocytes of Transgenic Mice That Model Glial Tauopathies. J. Neurosci. 25: 9434-9443 [Abstract] [Full Text]
Bjorkblom, B., Ostman, N., Hongisto, V., Komarovski, V., Filen, J.-J., Nyman, T. A., Kallunki, T., Courtney, M. J., Coffey, E. T. (2005). Constitutively Active Cytoplasmic c-Jun N-Terminal Kinase 1 Is a Dominant Regulator of Dendritic Architecture: Role of Microtubule-Associated Protein 2 as an Effector. J. Neurosci. 25: 6350-6361 [Abstract] [Full Text]
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]
Pickhardt, M., Gazova, Z., von Bergen, M., Khlistunova, I., Wang, Y., Hascher, A., Mandelkow, E.-M., Biernat, J., Mandelkow, E. (2005). Anthraquinones Inhibit Tau Aggregation and Dissolve Alzheimer's Paired Helical Filaments in Vitro and in Cells. J. Biol. Chem. 280: 3628-3635 [Abstract] [Full Text]
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]