IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
The frontotemporal dementia mutation R406W blocks tau's interaction with the membrane in an annexin A2-dependent manner.
Autor/es:
GAUTHIER-KEMPER A, .; WEISSMANN C, ; GOLOVYASHKINA N, ; SEBÖ-LEMKE Z, ; DREWES G, ; GERKE V, ; HEINISCH JJ, ; BRANDT R
Revista:
JOURNAL OF CELL BIOLOGY
Editorial:
ROCKEFELLER UNIV PRESS
Referencias:
Año: 2011 vol. 192 p. 647 - 661
ISSN:
0021-9525
Resumen:
Changes of the microtubule-associated protein tau are central in Alzheimer's
disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome
17 (FTDP-17). However, the functional consequence of the FTDP-17 tau mutation
R406W, which causes a tauopathy clinically resembling AD, is not well
understood. We find that the R406W mutation does not affect microtubule
interaction but abolishes tau's membrane binding. Loss of binding is associated
with decreased trapping at the tip of neurites and increased length fluctuations
during process growth. Tandem affinity purification tag purification and mass
spectrometry identify the calcium-regulated plasma membrane-binding protein
annexin A2 (AnxA2) as a potential interaction partner of tau. Consistently,
wild-type tau but not R406W tau interacts with AnxA2 in a heterologous yeast
expression system. Sequestration of Ca(2+) or knockdown of AnxA2 abolishes the
differential trapping of wild-type and R406W tau. We suggest that the
pathological effect of the R406W mutation is caused by impaired membrane
binding, which involves a functional interaction with AnxA2 as a
membrane-cytoskeleton linker.