Phosphorylation and dephosphorylation of tau protein by the catalytic subunit of PKA, as probed by electrophoretic mobility retard
Entity
UAM. Departamento de Química Física AplicadaPublisher
IOS PressDate
2020-12-29Citation
10.3233/JAD-201077
Journal of Alzheimers Disease 79.3 (2021): 1143-1156
ISSN
1387-2877 (print)DOI
10.3233/JAD-201077Funded by
Financial support has been provided by a grant from the Spanish Government PGC2018 096177-B-100Project
Gobierno de España. PGC2018-096177-B-100Editor's Version
https://doi.org/10.3233/JAD-201077Subjects
Dephosphorylation; Electrophoretic mobility; Phosphorylation; PKA; Tau protein; Thermodynamic reversibility; QuímicaRights
© 2021 – The authors. Published by IOS PressAbstract
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
Files in this item
Google Scholar:Benítez Moreno, María José
-
Cuadros, Raquel
-
Jiménez, Juan S.
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
Corrigendum to “Prostaglandin F2a-induced prostate transmembrane protein, androgen induced 1 mediates ovarian cancer progression increasing epithelial plasticity” [Neoplasia 21 (2019) 1073–1084]
Jiménez-Segovia, Alba; Mota, Alba; Rojo-Sebastián, Alejandro; Barrocal, Beatriz; Rynne-Vidal, Ángela; García-Bermejo, María Laura; Gómez-Bris, Raquel; Hawinkels, Lukas J A C; Sandoval, Pilar; García-Escudero, Ramón; López-Cabrera, Manuel; Moreno Bueno, Gema; Fresno Escudero, Manuel; Stamatakis Andriani, Konstantinos
2020-05