- Title
- Protein phosphatase 2A and tau: an orchestrated 'Pas de Deux'
- Creator
- Taleski, Goce; Sontag, Estelle
- Relation
- FEBS Letters Vol. 592, Issue 7, p. 1079-1095
- Publisher Link
- http://dx.doi.org/10.1002/1873-3468.12907
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2018
- Description
- The neuronal microtubule-associated protein tau serves a critical role in regu-lating axonal microtubule dynamics to support neuronal and synaptic func-tions. Furthermore, it contributes to glutamatergic regulation and synapticplasticity. Emerging evidence also suggests that tau serves as a signaling scaf-fold. Tau function and subcellular localization are tightly regulated, in part,by the orchestrated interplay between phosphorylation and dephosphorylationevents. Significantly, protein phosphatase type 2A (PP2A), encompassing theregulatory PPP2R2A (or Ba) subunit, is a major brain heterotrimeric enzymeand the primary tau Ser/Thr phosphatasein vivo. Herein, we closely examinehow the intimate and compartmentalized interactions between PP2A and tauregulate tau phosphorylation and function, and play an essential role in neu-ronal homeostasis. We also review evidence supporting a strong link betweenderegulation of tau–PP2A functional interactions and the molecular underpin-nings of various neurodegenerative diseases collectively called tauopathies.Lastly, we discuss the opportunities and associated challenges in more specifi-cally targeting PP2A–tau interactions for drug development for tauopathies.
- Subject
- dephosphorylation; PP2A; protein interactions; tau; tauopathies
- Identifier
- http://hdl.handle.net/1959.13/1440896
- Identifier
- uon:41253
- Identifier
- ISSN:0014-5793
- Language
- eng
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