Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells / drug effects
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3T3 Cells / metabolism
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3T3 Cells / pathology
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Alzheimer Disease / metabolism*
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Alzheimer Disease / physiopathology
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Animals
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Antimanic Agents / pharmacology
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Axons / metabolism*
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Axons / pathology
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Brain / metabolism*
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Brain / pathology
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Brain / physiopathology
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Calcium-Calmodulin-Dependent Protein Kinases / drug effects
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Colchicine / pharmacology
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Fluorescent Antibody Technique
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Gout Suppressants / pharmacology
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Green Fluorescent Proteins
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Indicators and Reagents / metabolism
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Lithium Chloride / pharmacology
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Luminescent Proteins / metabolism
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Mice
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Microtubules / drug effects
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Microtubules / metabolism*
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Microtubules / pathology
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Phosphorylation / drug effects
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Transfection
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Tubulin / metabolism
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tau Proteins / drug effects
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tau Proteins / genetics
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tau Proteins / metabolism*
Substances
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Antimanic Agents
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Gout Suppressants
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Indicators and Reagents
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Luminescent Proteins
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Tubulin
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tau Proteins
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Green Fluorescent Proteins
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Glycogen Synthase Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Lithium Chloride
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Colchicine