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Differential effect of three‐repeat and four‐repeat tau on mitochondrial axonal transport
Author(s) -
Stoothoff Will,
Jones Phillip B.,
SpiresJones Tara L.,
Joyner Daniel,
Chhabra Ekta,
Bercury Kathryn,
Fan Zhanyun,
Xie Hong,
Bacskai Brian,
Edd Jon,
Irimia Daniel,
Hyman Bradley T.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06316.x
Subject(s) - axoplasmic transport , gene isoform , neurodegeneration , axon , microtubule , biology , frontotemporal dementia , microbiology and biotechnology , neuroscience , genetics , dementia , gene , pathology , medicine , disease
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.