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PMID: 11901170 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 156 ·No. 6 ·2002-03-18 ·Pages 1051-63

Stamer K, Vogel R, Thies E, Mandelkow E, Mandelkow EM

Abstract

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.

MeSH Terms
Alzheimer Disease/metabolism,pathology,physiopathology Amyloid beta-Protein Precursor/genetics,metabolism Animals Brain/metabolism,pathology,physiopathology Cell Survival/genetics Cerebral Cortex/metabolism,pathology,physiopathology Chick Embryo Fluorescent Antibody Technique Gene Expression Regulation/physiology Golgi Apparatus/genetics,metabolism Humans Mice Mitochondria/genetics,metabolism Neurites/metabolism,pathology Neurofilament Proteins/genetics,metabolism Organelles/genetics,metabolism,pathology Oxidative Stress/genetics Peroxisomes/genetics,metabolism Protein Transport/genetics Rats Retinal Ganglion Cells/metabolism,pathology Time Factors Transport Vesicles/genetics,metabolism Tumor Cells, Cultured tau Proteins/genetics,metabolism
Chemicals
Amyloid beta-Protein Precursor Neurofilament Proteins tau Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Stamer K
Max-Planck-Unit for Structural Molecular Biology, 22607 Hamburg, Germany.
Vogel R
Thies E
Mandelkow E
Mandelkow E-M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200108057
Published
2002-03-18
Epub
2002-00-18
Pages
1051-63
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173473
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200108057 PMC Full Text View journal details
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