Tau--an inhibitor of deacetylase HDAC6 function.
Analysis of brain microtubule protein from patients with Alzheimer's disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.
Perez
Mar
M
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain.
Santa-Maria
Ismael
I
Gomez de Barreda
Elena
E
Zhu
Xiongwei
X
Cuadros
Raquel
R
Cabrero
Jose Roman
JR
Sanchez-Madrid
Francisco
F
Dawson
Hana N
HN
Vitek
Michael P
MP
Perry
George
G
Smith
Mark A
MA
Avila
Jesus
J
D000107:Acetylation / Q000187:drug effects; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011180:Postmortem Changes; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000172:deficiency / Q000378:metabolism*
D001897:Boronic Acids; D004791:Enzyme Inhibitors; C423917:MG 262; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D016875:tau Proteins; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases