Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport.
J Neurochem
; 111(2): 417-27, 2009 Oct.
Article
in En
| MEDLINE
| ID: mdl-19686388
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Axonal Transport
/
Tau Proteins
/
Tauopathies
/
Mitochondria
/
Neurons
Limits:
Animals
/
Humans
Language:
En
Journal:
J Neurochem
Year:
2009
Document type:
Article
Affiliation country:
Estados Unidos