Journal
EMBO JOURNAL
Volume 26, Issue 21, Pages 4546-4554Publisher
WILEY
DOI: 10.1038/sj.emboj.7601878
Keywords
axonal transport; dynactin; microtubule-binding; tau; tauopathies
Categories
Funding
- Alzheimers Research UK [ART-PG2004A-5, ART-RF2005-5] Funding Source: researchfish
- Medical Research Council [MC_U105184291, G0301152, MC_U105184313] Funding Source: researchfish
- MRC [G0301152, MC_U105184291, MC_U105184313] Funding Source: UKRI
- Medical Research Council [G0301152, U.1051.04.002(78842), MC_U105184313, MC_U105184291] Funding Source: Medline
Ask authors/readers for more resources
Tau is an axonal microtubule-associated protein involved in microtubule assembly and stabilization. Mutations in Tau cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and tau aggregates are present in Alzheimer's disease and other tauopathies. The mechanisms leading from tau dysfunction to neuro-degeneration are still debated. The dynein-activator complex dynactin has an essential role in axonal transport and mutations in its gene are associated with lower motor neuron disease. We show here for the first time that the N-terminal projection domain of tau binds to the C-terminus of the p150 subunit of the dynactin complex. Tau and dynactin show extensive colocalization, and the attachment of the dynactin complex to microtubules is enhanced by tau. Mutations of a conserved arginine residue in the N-terminus of tau, found in patients with FTDP-17, affect its binding to dynactin, which is abnormally distributed in the retinal ganglion cell axons of transgenic mice expressing human tau with a mutation in the microtubule-binding domain. These findings, which suggest a direct involvement of tau in axonal transport, have implications for understanding the pathogenesis of tauopathies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available