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GRK5 influences the phosphorylation of tau via GSK3β and contributes to Alzheimer's disease |
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| Authors: | Jianghao Zhao Xiaohui Li Xiongjin Chen Yujie Cai Yan Wang Wenjing Sun Hui Mai Jingqi Yang Weihao Fan Pei Tang Mingqian Ou Yuan Zhang Xuemei Huang Bin Zhao Lili Cui |
| Institution: | 1. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
Institute of Neurology, Dongguan People's Hospital, Dongguan, China Jianghao Zhao and Xiaohui Li contributed equally to this work.;2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China Jianghao Zhao and Xiaohui Li contributed equally to this work.;3. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;4. Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life, Science and Technology, Xi'an Jiaotong University, Xi'an, China;5. Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, China-America Cancer Research Institute, Guangdong Medical University, Dongguan, China;6. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;7. Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, China;8. School of Life Science and Technology, Harbin Institute of Technology, Harbin, China |
| 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. |
| Keywords: | Alzheimer's disease GRK5 GSK3β tau |