PMID- 17932487
OWN - NLM
STAT- MEDLINE
DCOM- 20071130
LR  - 20220309
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 26
IP  - 21
DP  - 2007 Oct 31
TI  - Interaction of tau protein with the dynactin complex.
PG  - 4546-54
AB  - 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.
FAU - Magnani, Enrico
AU  - Magnani E
AD  - Department of Clinical Neurosciences, Brain Repair Centre, University of 
      Cambridge, Cambridge, UK.
FAU - Fan, Juan
AU  - Fan J
FAU - Gasparini, Laura
AU  - Gasparini L
FAU - Golding, Matthew
AU  - Golding M
FAU - Williams, Meredith
AU  - Williams M
FAU - Schiavo, Giampietro
AU  - Schiavo G
FAU - Goedert, Michel
AU  - Goedert M
FAU - Amos, Linda A
AU  - Amos LA
FAU - Spillantini, Maria Grazia
AU  - Spillantini MG
LA  - eng
GR  - G0301152/MRC_/Medical Research Council/United Kingdom
GR  - MC_U105184291/MRC_/Medical Research Council/United Kingdom
GR  - MC_U105184313/MRC_/Medical Research Council/United Kingdom
GR  - U.1051.04.002(78842)/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071011
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Dynactin Complex)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (tau Proteins)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Animals
MH  - Arginine/chemistry
MH  - Axons/metabolism
MH  - Cloning, Molecular
MH  - Dynactin Complex
MH  - Humans
MH  - Mice
MH  - Microtubule-Associated Proteins/*chemistry/metabolism
MH  - Models, Biological
MH  - Mutation
MH  - Neurons/metabolism
MH  - Parkinsonian Disorders/genetics
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Two-Hybrid System Techniques
MH  - tau Proteins/chemistry/*physiology
PMC - PMC2063488
EDAT- 2007/10/13 09:00
MHDA- 2007/12/06 09:00
PMCR- 2008/10/31
CRDT- 2007/10/13 09:00
PHST- 2006/12/18 00:00 [received]
PHST- 2007/09/12 00:00 [accepted]
PHST- 2007/10/13 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/10/13 09:00 [entrez]
PHST- 2008/10/31 00:00 [pmc-release]
AID - 7601878 [pii]
AID - 10.1038/sj.emboj.7601878 [doi]
PST - ppublish
SO  - EMBO J. 2007 Oct 31;26(21):4546-54. doi: 10.1038/sj.emboj.7601878. Epub 2007 Oct 
      11.