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Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport.


ABSTRACT: Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4 repeat isoforms have not been studied. We examined the effects of tau on mitochondrial transport and found that both 3 repeat and 4 repeat tau change normal mitochondrial distribution within the cell body and reduce mitochondrial localization to axons; 4 repeat tau has a greater effect than 3 repeat tau. Further, we observed that the 3 repeat and 4 repeat tau cause different alterations in retrograde and anterograde transport dynamics with 3 repeat tau having a slightly stronger effect on axon transport dynamics. Our results indicate that tau-induced changes in axonal transport may be an underlying theme in neurodegenerative diseases associated with isoform specific changes in tau's interaction with microtubules.

SUBMITTER: Stoothoff W 

PROVIDER: S-EPMC2831412 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport.

Stoothoff Will W   Jones Phillip B PB   Spires-Jones Tara L TL   Joyner Daniel D   Chhabra Ekta E   Bercury Kathryn K   Fan Zhanyun Z   Xie Hong H   Bacskai Brian B   Edd Jon J   Irimia Daniel D   Hyman Bradley T BT  

Journal of neurochemistry 20090803 2


Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4 repeat isoforms have not been studied. We examined the effects of tau on mitochondrial transport and f  ...[more]

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