GRK5 influences the phosphorylation of tau via GSK3β and contributes to Alzheimer's disease. Issue 7 (3rd December 2018)

• Record Type: Journal Article
• Authors: Zhao, Jianghao; Li, Xiaohui; Chen, Xiongjin; Cai, Yujie; Wang, Yan; Sun, Wenjing; Mai, Hui; Yang, Jingqi; Fan, Weihao; Tang, Pei; Ou, Mingqian; Zhang, Yuan; Huang, Xuemei; Zhao, Bin; Cui, Lili
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 7(2019:Jul.)
• Page Start: 10411
• Page End: 10420
• Publication Date: 2018-12-03
• Subjects: Alzheimer's disease -- GRK5 -- GSK3β -- tau; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27709
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: G protein‐coupled receptor kinase 5 (GRK5) is a serine/threonine kinase whose dysfunction results in cognitive impairment and Alzheimer‐like pathology, including tau hyperphosphorylation. However, the mechanisms whereby GRK5 influences tau phosphorylation remain incompletely understood. In the current study, we showed that GRK5 influenced the phosphorylation of tau via glycogen synthase kinase 3β (GSK3β). The activity of both tau and GSK3β in the hippocampus was increased in aged GRK5‐knockout mice, which is consistent with what occurs in APP/PS1 transgenic mice. Furthermore, GRK5 regulated the activity of GSK3β and phosphorylated tau in vitro. Regardless of changes of GRK5 protein levels, tau hyperphosphorylation remained reduced after GSK3β activity was inhibited, suggesting that GRK5 may specifically influence tau hyperphosphorylation by modulating GSK3β activity. Taken together, our findings suggest that GRK5 deficiency contributes to the pathogenesis of Alzheimer's disease by influencing the hyperphosphorylation of tau through the activation of GSK3β. Abstract : 1. G protein‐coupled receptor kinase 5 (GRK5) regulates the activation of glycogen synthase kinase 3β (GSK3β) and p 396 tau in vitro. 2. Functional GRK5 negative correlated with activity of GSK3β and p 396 tau in Alzheimer's disease mouse model. 3. GRK5 deficiency induced tau hyperphosphorylation through GSK3β activation in vivo.