| Title | Proteome Profiling Identified Amyloid-beta Protein Precursor as a Novel Binding Partner and Modulator of VGLUT1 |
| Authors | Zhou, Jin-Wu Zhao, Man Rang, Wen-Liang Zhang, Xiao-Yan Liu, Zhen-Ming Zhang, Liang-Ren Wang, Tong-Xing Wu, Chu-Tse Cheng, Xiao-Rui Zhou, Wen-Xia |
| Affiliation | Tianjin Univ, Sch Chem Engn & Technol, Tianjin, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Dept Blood Transfus, Beijing, Peoples R China Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China Beijing Inst Pharmacol & Toxicol, Tai Ping Rd 27, Beijing 100850, Peoples R China State Key Lab Toxicol & Med Countermeasures, Beijing, Peoples R China |
| Keywords | GLUTAMATE TRANSPORTER EXPRESSION PREFRONTAL CORTEX ENDOPHILIN SYNAPSES RELEASE DECLINE |
| Issue Date | 2021 |
| Publisher | JOURNAL OF ALZHEIMERS DISEASE |
| Abstract | Background: The toxicity of excessive glutamate release has been implicated in various acute and chronic neurodegenerative conditions. Vesicular glutamate transporters (VGLUTs) are the major mediators for the uptake of glutamate into synaptic vesicles. However, the dynamics and mechanism of this process in glutamatergic neurons are still largely unknown. Objective: This study aimed to investigate the candidate protein partners of VGLUT1 and their regulatory roles in the vesicles in rat brain. Methods: Pull down assay, co-immunoprecipitation assay, or split-ubiquitin membrane yeast two hybrid screening coupled with nano RPLC-MS/MS were used to identify the candidate protein partners of VGLUT1 in the vesicles in rat brain. The in vitro and in vivo models were used to test effects of A beta PP, Atp6ap2, Gja1, and Synataxin on VGLUT1 expression. Results: A total of 255 and 225 proteins and 172 known genes were identified in the pull down assay, co-immunoprecipitation assay, or split-ubiquitin yeast two-hybrid screening respectively. The physiological interactions of SV2A, Syntaxin 12, Gja1, A beta PP, and Atp6ap2 to VGLUT1 were further confirmed. Knockdown of Atp6ap2, Gja1, and Synataxin increased VGLUT1 mRNA expression and only knockdown of A beta PP increased both mRNA and protein levels of VGLUT1 in PC12 cells. The regulatory function of A beta PP on VGLUT1 expression was further confirmed in the in vitro and in vivo models. Conclusion: These results elucidate that the A beta PP and VGLUT1 interacts at vesicular level and A beta PP plays a role in the regulation of VGLUT1 expression which is essential for maintaining vesicular activities. |
| URI | http://hdl.handle.net/20.500.11897/617588 |
| ISSN | 1387-2877 |
| DOI | 10.3233/JAD-210117 |
| Indexed | SCI(E) |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
