Phosphorylation and Dephosphorylation of Tau Protein by the Catalytic Subunit of PKA, as Probed by Electrophoretic Mobility Retard
| Autor: | María J. Benítez, Juan S. Jiménez, Raquel Cuadros |
|---|---|
| Přispěvatelé: | UAM. Departamento de Química Física Aplicada, Ministerio de Ciencia e Innovación (España) |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microtubule-associated protein Protein subunit Tau protein Phosphatase Thermodynamic reversibility Electrophoretic Mobility Shift Assay tau Proteins Catalysis Dephosphorylation 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Electrophoretic mobility Animals Humans PKA Phosphorylation chemistry.chemical_classification Cyclic AMP-Dependent Protein Kinase Catalytic Subunits biology Kinase General Neuroscience Química General Medicine Adenosine Diphosphate Psychiatry and Mental health Clinical Psychology 030104 developmental biology Enzyme chemistry biology.protein Biophysics Cattle Electrophoresis Polyacrylamide Gel Geriatrics and Gerontology 030217 neurology & neurosurgery Research Article |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM instname Digital.CSIC. Repositorio Institucional del CSIC Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-201077 |
| Popis: | Background: Tau is a microtubule associated protein that regulates the stability of microtubules and the microtubule-dependent axonal transport. Its hyperphosphorylated form is one of the hallmarks of Alzheimer's disease and other tauopathies and the major component of the paired helical filaments that form the abnormal proteinaceous tangles found in these neurodegenerative diseases. It is generally accepted that the phosphorylation extent of tau is the result of an equilibrium in the activity of protein kinases and phosphatases. Disruption of the balance between both types of enzyme activities has been assumed to be at the origin of tau hyperphosphorylation and the subsequent toxicity and progress of the disease. Objective: We explore the possibility that, beside the phosphatase action on phosphorylated tau, the catalytic subunit of PKA catalyzes both tau phosphorylation and also tau dephosphorylation, depending on the ATP/ADP ratio. Methods: We use the shift in the relative electrophoretic mobility suffered by different phosphorylated forms of tau, as a sensor of the catalytic action of the enzyme. Results: The results are in agreement with the long-known thermodynamic reversibility of the phosphorylation reaction (ATP + Protein = ADP+Phospho-Protein) catalyzed by PKA and many other protein kinases. Conclusion: The results contribute to put the compartmentalized energy state of the neuron and the mitochondrial-functions disruption upstream of tau-related pathologies. Spanish Government PGC2018 096177-B_100 |
| Databáze: | OpenAIRE |
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