Phosphorylation of tau by glycogen synthase kinase 3beta in intact mammalian cells influences the stability of microtubules.
Tau is a neuronal microtubule-associated protein found predominantly in axons. Hyperphosphorylation of tau reduces the stability of microtubules, which may be a pathogenic mechanism in Alzheimer's disease. To understand the different effects between tau and glycogen synthase kinase 3beta (GSK-3beta) phosphorylated tau on the organization and stability of microtubules, we performed transfection studies on 3T3 cells using EGFP-tau (Enhanced Green Fluorescence Protein-tau) and GSK-3beta to quantify the stability of microtubules. Laser confocal microscope observation revealed that thick and thin microtubule bundles could be induced by tau and GSK-3beta phosphorylated tau. The bundles appeared either to be relatively straight or to form a ring around the circumference of the cell. Both the thick and thin microtubule bundles were resistant to colchicine-induced dissociation, with thick bundles more resistant than thin bundles. The bundles induced by GSK-3beta phosphorylated tau were sensitive to colchicine, and could be reversed by the addition of LiCl, an inhibitor of GSK-3beta.
Sang
H
H
Department of Cell Biology and Genetics, College of Life Science, Peking University, Beijing 100871, China.
Lu
Z
Z
Li
Y
Y
Ru
B
B
Wang
W
W
Chen
J
J
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006074:Gout Suppressants / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D018692:Antimanic Agents; D006074:Gout Suppressants; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D014404:Tubulin; D016875:tau Proteins; D049452:Green Fluorescent Proteins; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride; D003078:Colchicine