Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: Implications for Alzheimer’s disease
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The neuronal microtubule-associated protein tau plays an important role in establishing cell polarity by stabilizing axonal microtubules that serve as tracks for motor-protein–driven transport processes. To investigate the role of tau in intracellular transport, we studied the effects of tau expression in stably transfected CHO cells and differentiated neuroblastoma N2a cells. Tau causes a change in cell shape, retards cell growth, and dramatically alters the distribution of various organelles, known to be transported via microtubule-dependent motor proteins. Mitochondria fail to be transported to peripheral cell compartments and cluster in the vicinity of the microtubule-organizing center. The endoplasmic reticulum becomes less dense and no longer extends to the cell periphery. In differentiated N2a cells, the overexpression of tau leads to the disappearance of mitochondria from the neurites. These effects are caused by tau's binding to microtubules and slowing down intracellular transport by preferential impairment of plus-end–directed transport mediated by kinesin-like motor proteins. Since in Alzheimer's disease tau protein is elevated and mislocalized, these observations point to a possible cause for the gradual degeneration of neurons.
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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 [21]
The Results sections report slowed outward trafficking of exocytic vesicles and a reduced, perinuclear vimentin network in tau-overexpressing CHO cells (pages unavailable). In differentiated N2a cells, the paper reports impaired transport of mitochondria and endoplasmic reticulum into neurites, but does not establish the claimed vesicle-trafficking or intermediate-filament effects in those cells. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTau 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 Ebneth et al., 1998
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 Ebneth et al., 1998
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- Authors
- Ebneth, A., Godemann, R., Stamer, K., Illenberger, S., Trinczek, B., Mandelkow, E.-M., & Mandelkow, E.
- Affiliations
- Max Planck Unit for Structural Molecular Biology (DE)
- Max-Planck Unit for Structural Molecular Biology, D-22607 Hamburg, Germany
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1998-11-02
- Volume
- 143
- Issue
- 3
- Pages
- 777-794
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2148132
- OpenAlex
- W1975321314
- Cited by
- 820
- References
- 1
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 17 · 2023: 30 · 2022: 28 · 2021: 28 · 2020: 36 · 2019: 31 · 2018: 34 · 2017: 25 · 2016: 42 · 2015: 26 · 2014: 35 · 2013: 29 · 2012: 36
- FWCI
- 14.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Cell
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tau protein, kinesin, intracellular transport, mitochondrial transport, vesicle trafficking, microtubule binding, Alzheimer's disease, neurodegeneration, axonal microtubules, organelle distribution
- MeSH terms
- Docetaxel, Alzheimer Disease, Animals, Biological Transport, Dyneins, Endoplasmic Reticulum, Cricetinae, Intermediate Filament Proteins, Microinjections, Mitochondria, Transferrin, Tumor Cells, Cultured, Nocodazole, Gene Expression, CHO Cells, Kinesins, tau Proteins, Paclitaxel, Centrosome, Taxoids, Cell Size
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