Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles
Abstract
We have performed a real time analysis of fluorescence-tagged vesicle and mitochondria movement in living CHO cells transfected with microtubule-associated protein tau or its microtubule-binding domain. Tau does not alter the speed of moving vesicles, but it affects the frequencies of attachment and detachment to the microtubule tracks. Thus, tau decreases the run lengths both for plus-end and minus-end directed motion to an equal extent. Reversals from minus-end to plus-end directed movement of single vesicles are strongly reduced by tau, but reversals in the opposite direction (plus to minus) are not. Analogous effects are observed with the transport of mitochondria and even with that of vimentin intermediate filaments. The net effect is a directional bias in the minus-end direction of microtubules which leads to the retraction of mitochondria or vimentin IFs towards the cell center. The data suggest that tau can control intracellular trafficking by affecting the attachment and detachment cycle of the motors, in particular by reducing the attachment of kinesin to microtubules, whereas the movement itself is unaffected.
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Overexpression of Tau in CHO cells and N2a neuroblastoma cells inhibits kinesin-dependent trafficking of vesicles and disturbs the organization of intermediate filaments.
“In contrast, other reports on Chinese hamster ovary (CHO) cells [21, 22] and N2a neuroblastoma cells [23] concluded that overexpression of Tau inhibits kinesin-dependent trafficking of vesicles and disturbs the organization of intermediate filaments.”
From Expression of Tau Produces Aberrant Plasma Membrane Blebbing in Glial Cells Through RhoA-ROCK-Dependent F-Actin Remodeling (2016) · cites this paper as [22]
Overexpression of Tau inhibits mitochondrial transport in various cells.
“Overexpression of Tau inhibits mitochondrial transport in various cells (Ebneth et al., 1998;Trinczek et al., 1999;Stamer et al., 2002;Dixit et al., 2008;Stoothoff et al., 2009;Vossel et al., 2010).”
From Regulation of Mitochondrial Transport and Inter-Microtubule Spacing by Tau Phosphorylation at the Sites Hyperphosphorylated in Alzheimer's Disease (2012) · cites this paper as Trinczek et al., 1999
Tau overexpression inhibits mitochondrial movement in various cell types.
“Tau overexpression inhibits mitochondrial movement in various cell types (Ebneth et al., 1998;Trinczek et al., 1999;Stamer et al., 2002;Dixit et al., 2008;Stoothoff et al., 2009;Vossel et al., 2010).”
From Regulation of Mitochondrial Transport and Inter-Microtubule Spacing by Tau Phosphorylation at the Sites Hyperphosphorylated in Alzheimer's Disease (2012) · cites this paper as Trinczek et al., 1999
Cites
Tanaka, Y., Kanai, Y., Okada, Y., Nonaka, S., Takeda, S., Harada, A., & Hirokawa, N. (1998) · Cell · doi:10.1016/s0092-8674(00)81459-2 · Cited by 654 · see citing works
Kanai, Y., & Hirokawa, N. (1995) · Neuron · doi:10.1016/0896-6273(95)90298-8 · Cited by 144 · see citing works
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Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Differential Regulation of Dynein and Kinesin Motor Proteins by Tau
Dixit, R., Ross, J. L., Goldman, Y. E., & Holzbaur, E. L. F. (2008) · Science · doi:10.1126/science.1152993 · Cited by 1,012 · see citing works
Tau is essential to β-amyloid-induced neurotoxicity
Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., & Ferreira, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092136199 · Cited by 807 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Traffic control: regulation of kinesin motors
Verhey, K. J., & Hammond, J. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2782 · Cited by 546 · see citing works
Tau filament formation in transgenic mice expressing P301L tau
Götz, J., Chen, F., Barmettler, R., & Nitsch, R. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006531200 · Cited by 495 · see citing works
Near-atomic model of microtubule-tau interactions
Kellogg, E. H., Hejab, N. M. A., Poepsel, S., Downing, K. H., DiMaio, F., & Nogales, E. (2018) · Science · doi:10.1126/science.aat1780 · Cited by 416 · see citing works
Glial contributions to neurodegeneration in tauopathies
Leyns, C. E. G., & Holtzman, D. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0192-x · Cited by 409 · see citing works
MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments
Al-Bassam, J., Ozer, R. S., Safer, D., Halpain, S., & Milligan, R. A. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200201048 · Cited by 327 · see citing works
GSK-3β inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila
Mudher, A., Shepherd, D., Newman, T. A., Mildren, P., Jukes, J. P., Squire, A., Mears, A., Berg, S., MacKay, D., Asuni, A. A., et al. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001483 · Cited by 265 · see citing works
Single-molecule investigation of the interference between kinesin, tau and MAP2c
Seitz, A., Kojima, H., Oiwa, K., Mandelkow, E.-M., Song, Y.-H., & Mandelkow, E. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf503 · Cited by 257 · see citing works
Self-citationKinesin Assembly and Movement in Cells
Verhey, K. J., Kaul, N., & Soppina, V. (2011) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-042910-155310 · Cited by 231 · see citing works
Shahpasand, K., Uemura, I., Saito, T., Asano, T., Hata, K., Shibata, K., Toyoshima, Y., Hasegawa, M., & Hisanaga, S.-I. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5927-11.2012 · Cited by 206 · see citing works
Nuclear Tau and Its Potential Role in Alzheimer’s Disease
Bukar Maina, M., Al-Hilaly, Y., & Serpell, L. (2016) · Biomolecules · doi:10.3390/biom6010009 · Cited by 161 · see citing works
Cowan, C. M., Bossing, T., Page, A., Shepherd, D., & Mudher, A. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0716-8 · Cited by 156 · see citing works
Differential effect of three‐repeat and four‐repeat tau on mitochondrial axonal transport
Stoothoff, W., Jones, P. B., Spires‐Jones, T. L., Joyner, D., Chhabra, E., Bercury, K., Fan, Z., Xie, H., Bacskai, B., Edd, J., et al. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06316.x · Cited by 135 · see citing works
Traffic at the intersection of neurotrophic factor signaling and neurodegeneration
Salehi, A., Delcroix, J.-D., & Mobley, W. C. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)00038-3 · Cited by 131 · see citing works
Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
Microtubule lattice spacing governs cohesive envelope formation of tau family proteins
Siahaan, V., Tan, R., Humhalova, T., Libusova, L., Lacey, S. E., Tan, T., Dacy, M., Ori-McKenney, K. M., McKenney, R. J., Braun, M., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01096-2 · Cited by 94 · see citing works
The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
Transcriptional and conformational changes of the tau molecule in Alzheimer's disease
Hyman, B. T., Augustinack, J. C., & Ingelsson, M. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.06.015 · Cited by 79 · see citing works
Yoshiyama, Y., Zhang, B., Bruce, J., Trojanowski, J. Q., & Lee, V. M.-Y. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-33-10662.2003 · Cited by 72 · see citing works
Mitochondrial dynamics in aging and disease
Bereiter-Hahn, J. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-394625-6.00004-0 · Cited by 48 · see citing works
Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease
Li, X., Tsolis, K. C., Koper, M. J., Ronisz, A., Ospitalieri, S., von Arnim, C. A. F., Vandenberghe, R., Tousseyn, T., Scheuerle, A., Economou, A., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12345 · Cited by 27 · see citing works
Torres-Cruz, F. M., Rodríguez-Cruz, F., Escobar-Herrera, J., Barragán-Andrade, N., Basurto-Islas, G., Ripova, D., Ávila, J., & Garcia-Sierra, F. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150396 · Cited by 19 · see citing works
Nakata, R., Torii, T., Miyasaka, T., & Misonou, H. (2026) · Neuroscience Research · doi:10.1016/j.neures.2025.104987 · Cited by 3 · see citing works
- Authors
- Trinczek, B., Ebneth, A., Mandelkow, E.-M., & Mandelkow, E.
- Affiliations
- Max Planck Unit for Structural Molecular Biology (DE)
- Max-Planck Unit for Structural Molecular Biology, Notkestrasse 85, D-22607 Hamburg, Germany
- Corresponding author
- Trinczek, B.
- Ebneth, A.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 1999-07-15
- Volume
- 112
- Issue
- 14
- Pages
- 2355-2367
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2153578959
- Cited by
- 344
- References
- 2
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 5 · 2023: 10 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 14 · 2018: 12 · 2017: 15 · 2016: 20 · 2015: 16 · 2014: 21 · 2013: 11 · 2012: 14
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- tau protein, microtubule transport, kinesin, vesicle trafficking, mitochondrial transport, vimentin intermediate filaments, intracellular trafficking, run length, directional bias, microtubule-binding domain, CHO cells
- MeSH terms
- Animals, Binding Sites, Biological Transport, Active, Exocytosis, Fluorescent Dyes, Cricetinae, Humans, Intermediate Filaments, Microtubules, Movement, Peptide Fragments, Recombinant Proteins, Transfection, Vimentin, Organelles, CHO Cells, Kinesins, tau Proteins, Molecular Motor Proteins
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