Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1

Sun, Miao; Zhang, Huaye

doi:10.1016/j.neurobiolaging.2017.08.024

Cited by 24 publications

(33 citation statements)

References 93 publications

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“…Increasing the convergence of APP and BACE1 and retaining the enzyme in acidic compartments when activated [120]…”

Section: Discussionmentioning

confidence: 99%

“…Afterwards, BACE1 molecules are delivered to the cell surface or to cell compartments where the APP cleavage occurs and may affect the generation of Aβ. Indeed, Sun et al discovered a significant decrease in the S498 phosphorylation of BACE1 in AD patients [120]. Their study also proved that the polarity protein Par3 regulates the retrograde trafficking of BACE1 from the endosome to the TGN by atypical PKC (aPKC)-mediated S498 phosphorylation.…”

Section: β-Secretase Phosphorylationmentioning

confidence: 94%

“…Their study also proved that the polarity protein Par3 regulates the retrograde trafficking of BACE1 from the endosome to the TGN by atypical PKC (aPKC)-mediated S498 phosphorylation. The absence of Par3 reduces the S498 phosphorylation of BACE1, increases the convergence of APP and BACE1, and retains the enzyme in acidic compartments such as endosomes/lysosomes, in which the β-secretase cleavage of APP usually takes place [120,121]. CDK5 dysregulation has been implicated in AD.…”

Section: β-Secretase Phosphorylationmentioning

confidence: 99%

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Phosphorylation Signaling in APP Processing in Alzheimer’s Disease

Zhang

Chen

Lee

2019

IJMS

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The abnormal accumulation of amyloid-β (Aβ) in the central nervous system is a hallmark of Alzheimer's disease (AD). The regulation of the processing of the single-transmembrane amyloid precursor protein (APP) plays an important role in the generation of Aβ in the brain. The phosphorylation of APP and key enzymes involved in the proteolytic processing of APP has been demonstrated to be critical for modulating the generation of Aβ by either altering the subcellular localization of APP or changing the enzymatic activities of the secretases responsible for APP processing. In addition, the phosphorylation may also have an impact on the physiological function of these proteins. In this review, we summarize the kinases and signaling pathways that may participate in regulating the phosphorylation of APP and secretases and how this further affects the function and processing of APP and Aβ pathology. We also discuss the potential of approaches that modulate these phosphorylation-signaling pathways or kinases as interventions for AD pathology.

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“…Increasing the convergence of APP and BACE1 and retaining the enzyme in acidic compartments when activated [120]…”

Section: Discussionmentioning

confidence: 99%

Section: β-Secretase Phosphorylationmentioning

confidence: 94%

Section: β-Secretase Phosphorylationmentioning

confidence: 99%

See 1 more Smart Citation

Phosphorylation Signaling in APP Processing in Alzheimer’s Disease

Zhang

Chen

Lee

2019

IJMS

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“…Disruption of other retromer components, VPS26 and VPS35, blocks BACE-1 retrograde transport (He et al, 2005;Wen et al, 2011). Also, the sorting proteins GGA and PACS1, which mediate protein trafficking between TGN and endosomes, interacts with cytosolic dileucine motif of BACE-1 for its retrieval trafficking (Wan et al, 1998;Bonifacino, 2004;He et al, 2005;Sun and Zhang, 2017). The interaction between BACE-1 and these sorting proteins requires the phosphorylation of BACE-1 at Serine 498 by casein kinase 1 and aPKC/Par3 complex (Walter et al, 2001;von Arnim et al, 2004;Sun and Zhang, 2017).…”

Section: Key Regulators Of App/bace-1 Sorting/retrieval In Amyloidogementioning

confidence: 99%

The physical approximation of APP and BACE‐1: A key event in alzheimer's disease pathogenesis

Sun

Roy

2017

Developmental Neurobiology

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Alzheimer's disease (AD) is characterized by the accumulation of insoluble deposits of Amyloid β (Aβ) in brains. Aβ is derived by sequential cleavage of the amyloid precursor protein (APP) by β-site secretase enzyme (BACE-1) and γ-secretase. Proteolytic processing of APP by BACE-1 is the rate-limiting step in Aβ production, and this pathway is a prime target for AD drug development. Both APP and BACE-1 are membrane-spanning proteins, transported via secretory and endocytic pathways; and the physical interaction of APP and BACE-1 during trafficking is a key cell biological event initiating the amyloidogenic pathway. Here, we highlight recent research on intracellular trafficking/sorting of APP and BACE-1, and discuss how dysregulation of these pathways might lead to enhanced convergence of APP and BACE-1, and subsequent β-cleavage of APP. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 340-347, 2018.

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“…Cells were then stained with crystal violet. Results represented the mean of counting in three different areas under light microscope (magnification, x40), according to a previous study (17).…”

Section: Introductionmentioning

confidence: 99%

Corosolic acid impairs human lung adenocarcinoma A549 cells proliferation by inhibiting cell migration

Wang

et al. 2019

Oncol Lett

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The present study aimed to investigate the anticancer effects of corosolic acid (CA) in the human lung adenocarcinoma A549 cell line. A549 cells were treated with increasing concentrations of CA, prior to assessing cell viability, migration rate, vascular endothelial growth factor receptor 2 (VEGFR2) kinase activity and cytoskeleton structure. In addition, in vivo imaging system was used to analyze the anticancer effects of CA in vivo. Results demonstrated that CA exhibited a low cytotoxicity with a half maximal inhibitory concentration of 65 µM. In addition, 4 µM CA efficiently inhibited A549 cell migration. Furthermore, CA inhibited VEGFR2 kinase activity and disrupted tubulin structure. Data also revealed that CA inhibited A549 cell proliferation in a xenograft mouse model. In conclusion, results from the present study suggested that CA may be used as a novel potential therapy for lung cancer. Materials and methods Cell line and reagents. The A549 cell line was purchased from National Infrastructure of Cell Line Resource (Beijing, China)

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Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1

Cited by 24 publications

References 93 publications

Phosphorylation Signaling in APP Processing in Alzheimer’s Disease

Phosphorylation Signaling in APP Processing in Alzheimer’s Disease

The physical approximation of APP and BACE‐1: A key event in alzheimer's disease pathogenesis

Corosolic acid impairs human lung adenocarcinoma A549 cells proliferation by inhibiting cell migration

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