Article
- The EMBO Journal (2007) 26, 4546 - 4554
- doi:10.1038/sj.emboj.7601878
Published online: 11 October 2007
Subject Categories:
Interaction of tau protein with the dynactin complex
Enrico Magnani1,a, Juan Fan2,a, Laura Gasparini1, Matthew Golding3, Meredith Williams1, Giampietro Schiavo3, Michel Goedert2, Linda A Amos2 and Maria Grazia Spillantini1
- Department of Clinical Neurosciences, Brain Repair Centre, University of Cambridge, Cambridge, UK
- Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
- Cancer Research UK London Research Institute, London, UK
Correspondence to:
Maria Grazia Spillantini, Department of Clinical Neurosciences, Brain Repair Centre, University of Cambridge, Robinson way, Forvie site, Cambridge CB2 0PY, UK. Tel.: +44 1223 331145; Fax +44 1223 331174; E-mail: mgs11@cam.ac.uk
aThese authors contributed equally to this work
Received 18 December 2006; Accepted 12 September 2007
Abstract
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 neurodegeneration 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.
Keywords:
- axonal transport,
- dynactin,
- microtubule-binding,
- tau,
- tauopathies
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