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

被引：723

作者：

Stamer, K ^{[1
]}

Vogel, R ^{[1
]}

Thies, E ^{[1
]}

Mandelkow, E ^{[1
]}

Mandelkow, EM ^{[1
]}

机构：

[1] Max Planck Unit Struct Mol Biol, D-22607 Hamburg, Germany

来源：

JOURNAL OF CELL BIOLOGY | 2002年 / 156卷 / 06期

关键词：

axonal traffic; microtubules; tau protein; amyloid precursor protein; oxidative stress;

D O I：

10.1083/jcb.200108057

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (similar to80%) and slowly back (similar to20%). 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.

引用

页码：1051 / 1063

页数：13

共 70 条

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