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Interaction of tau protein with the dynactin complex
Author(s) -
Magnani Enrico,
Fan Juan,
Gasparini Laura,
Golding Matthew,
Williams Meredith,
Schiavo Giampietro,
Goedert Michel,
Amos Linda A,
Spillantini Maria Grazia
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601878
Subject(s) - brain research , research centre , library science , art history , history , biology , neuroscience , computer science
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.