Phosphorylated, but not native, tau protein assembles following reaction with the lipid peroxidation product, 4-hydroxy-2-nonenal.
A correlation between hyperphosphorylation of tau protein and its aberrant assembly into paired helical filaments has lead to suggestions that phosphorylation controls assembly, but lacked a mechanistic basic. In this work, we have found that phosphorylated, but not native, tau protein is able to form polymers after the reaction with 4-hydroxy-2-nonenal, a highly toxic product of lipid peroxidation. Phosphorylation of tau by both proline or non-proline directed kinases, was able to assemble it into polymers.
Pérez
M
M
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
Cuadros
R
R
Smith
M A
MA
Perry
G
G
Avila
J
J
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D019319:Okadaic Acid / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D016875:tau Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D000447:Aldehydes; D004791:Enzyme Inhibitors; D010455:Peptides; D016875:tau Proteins; D019319:Okadaic Acid; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010744:Phosphoric Monoester Hydrolases; C027576:4-hydroxy-2-nonenal