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Synaptic Vesicle Glycoprotein 2A Slows down Amyloidogenic Processing of Amyloid Precursor Protein via Regulating Its Intracellular Trafficking

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收录情况: ◇ 统计源期刊 ◇ 卓越:梯队期刊

机构: [1]Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing 100053, China [2]Department of Clinical Laboratory, Changzhi People’s Hospital of Changzhi Medical College, Changzhi 046000, Shanxi, China
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To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation.Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing.APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ 1-42, and Aβ 1-40, were decreased in SV2A-overexpressed cells.These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.Copyright © 2025 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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出版当年[2025]版:
大类 | 4 区 医学
小类 | 4 区 环境科学 4 区 公共卫生、环境卫生与职业卫生
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 环境科学 4 区 公共卫生、环境卫生与职业卫生
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第一作者机构: [1]Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing 100053, China
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