Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress.
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 (approximately 80%) and slowly back (approximately 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.
Stamer
K
K
Max-Planck-Unit for Structural Molecular Biology, 22607 Hamburg, Germany.
Vogel
R
R
Thies
E
E
Mandelkow
E
E
Mandelkow
E-M
EM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002642:Chick Embryo; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism* / Q000473:pathology; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D015388:Organelles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D016900:Neurofilament Proteins; D016875:tau Proteins