Regulatory role of Golgi brefeldin A resistance factor‐1 in amyloid precursor protein trafficking, cleavage and Aβ formation

2019 ◽  
Vol 120 (9) ◽  
pp. 15604-15615 ◽  
Author(s):  
Kaifei Liu ◽  
Ying Liu ◽  
Yanting Xu ◽  
Kutty Selva Nandakumar ◽  
Xiaoyan Shen ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Trafficking ◽  
Brefeldin A ◽  
Resistance Factor ◽  
Precursor Protein ◽  
Regulatory Role ◽  
Amyloid Precursor Protein Trafficking

scholarly journals GGA1 Acts as a Spatial Switch Altering Amyloid Precursor Protein Trafficking and Processing

2006 ◽  
Vol 26 (39) ◽  
pp. 9913-9922 ◽  
Author(s):  
C. A. F. von Arnim ◽  
R. Spoelgen ◽  
I. D. Peltan ◽  
M. Deng ◽  
S. Courchesne ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Trafficking ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Trafficking

scholarly journals Alix and Syntenin-1 direct amyloid precursor protein trafficking into extracellular vesicles

2020 ◽  
Author(s):  
Allaura S. Cone ◽  
Stephanie N. Hurwitz ◽  
Glorida S. Lee ◽  
Xuegang Yuan ◽  
Yi Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Subcellular Localization ◽  
Amyloid Precursor Protein ◽  
Extracellular Vesicles ◽  
Protein Trafficking ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Trafficking

Abstract Background: Endosomal trafficking and amyloidogenic cleavage of amyloid precursor protein (APP) is believed to play a role in the neurodegeneration observed in Alzheimer’s disease (AD). Recent evidence has suggested that packaging and secretion of APP and its amyloidogenic cleaved product (βAPP) into small extracellular vesicles (EVs) may facilitate uptake of these neurotoxic factors during disease progression. However, the molecular mechanisms underlying trafficking of APP into EVs are poorly understood. Results: In this study, the mechanism and impact of amyloid precursor protein trafficking into extracellular vesicles (EVs) were assessed by a series of inducible gene knockdowns. We demonstrate that vesicle-associated proteins Alix and Syntenin-1 are essential for proper subcellular localization and efficient EV secretion of APP via an endosomal sorting complexes required for transport (ESCRT)-independent pathway. The neurotoxic C-terminal fragment (CTF) of APP is similarly secreted in association with small vesicles. These mechanisms are conserved in terminally differentiated neuron-like cells. Furthermore, knockdown of Alix and Syntenin-1 alters the subcellular localization of APP, sequestering the precursor protein to endoplasmic reticulum and endolysosomal compartments, respectively. Finally, transfer of small EVs containing APP confers an increase in reactive oxygen species production and neurotoxicity to human induced pluripotent stem cell-derived cortical neurons and naïve primary neurons, an effect that is ameliorated by Alix and Syntenin-1 depletion. Conclusions: Altogether these findings elucidate a novel mechanism for understanding the intracellular trafficking of APP and βAPP into secreted extracellular vesicles, and the resultant potential impact on neurotoxicity in the context of Alzheimer’s disease amyloidopathy.

Memantine reduces the production of amyloid-β peptides through modulation of amyloid precursor protein trafficking

2017 ◽  
Vol 798 ◽  
pp. 16-25 ◽  
Author(s):  
Kaori Ito ◽  
Takuya Tatebe ◽  
Kunimichi Suzuki ◽  
Takashi Hirayama ◽  
Maki Hayakawa ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Trafficking ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Trafficking

Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA

2017 ◽  
Vol 75 (2) ◽  
pp. 301-322 ◽  
Author(s):  
Simone Eggert ◽  
A. C. Gonzalez ◽  
C. Thomas ◽  
S. Schilling ◽  
S. M. Schwarz ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Trafficking ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Trafficking
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