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

By K. Stamer, R. Vogel, E. Thies, E. Mandelkow. Journal of Cell Biology, 2002

919 citations recorded by the source corpus.

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 (∼80%) and slowly back (∼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.

Subfields: Cell Biology, Cellular and Molecular Neuroscience, Physiology

View Paper: https://www.semanticscholar.org/paper/a7376505627c08dd8721e462807ec773b7fd4412

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. R. Vale
2. E. Mandelkow
3. W. Saxton
4. P. Hollenbeck
5. N. Hirokawa
6. Shinsuke Niwa
7. Yosuke Tanaka

In Cellular and Molecular Neuroscience

1. R. Vale
2. E. Mandelkow
3. Christian Haass
4. Sangram S. Sisodia
5. D. Holtzman
6. J. Long

In Physiology

1. R. Vale
2. E. Mandelkow
3. E. Thies
4. Yan Zhao
5. H. Zempel
6. Christian Haass
7. Sangram S. Sisodia
8. Baolu Zhao

Citations in the corpus

• The molecular motor toolbox for intracellular transport. (2003, positive): “A knockout of the mouse ortholog, KIF1A, produced a similar phenotype (Yonekawa et al., 1998).”
• Mitochondrial dysfunction - the beginning of the end in Alzheimer's disease? Separate and synergistic modes of tau and amyloid-β toxicity (2011, background): “Mitochondria and tau protein How does tau interfere with mitochondrial function? In its hyperphosphorylated form, tau, which forms the second hallmark lesion in AD, the NFTs, has been shown to block mitochondrial transport, which results in energy deprivation and oxidative stress at the synapse and,”
• The axonal transport of mitochondria (2005, background): “In neuroblastoma cells and retinal ganglion cells, a high concentration of a non-phosphorylated tau isoform has been shown to alter the transport of mitochondria and other organelles, thereby limiting their presence in neurites (Mandelkow et al., 2004; Ebneth et al., 1998; Stamer et al., 2002).”
• Oxidative Stress and the Pathogenesis of Alzheimer's Disease (2013, background): “It was also shown that the cells overexpressing tau protein had increased susceptibility against oxidative stress, perhaps due to the depletion of peroxisomes [123].”
• Structural Polymorphism of 441-Residue Tau at Single Residue Resolution (2009, background): “, interaction with motor proteins of axonal transport [67]).”
• Trafficking and proteolytic processing of APP. (2012, background): “As visualized by GFP-tagged fusion proteins, APP is transported in vesicular and often elongated tubular structures which move with special characteristics along the axon (Kaether et al. 2000; Stamer et al. 2002; Goldsbury et al. 2006; Szodorai et al. 2009).”