Phosphorylation and Dephosphorylation of Tau Protein by the Catalytic Subunit of PKA, as Probed by Electrophoretic Mobility Retard.
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.
['Benítez|María J|MJ|', 'Cuadros|Raquel|R|', 'Jiménez|Juan S|JS|']
D000244:Adenosine Diphosphate D000255:Adenosine Triphosphate D000818:Animals D002384:Catalysis D002417:Cattle D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits D004591:Electrophoresis, Polyacrylamide Gel D024202:Electrophoretic Mobility Shift Assay D006801:Humans D010766:Phosphorylation D016875:tau Proteins
phosphorylation Dephosphorylation tau protein PKA electrophoretic mobility thermodynamic reversibility