3′UTR enhances hCD47 cell surface expression, self‐signal function, and reduces ER stress in porcine fibroblasts

2020 ◽  
Author(s):  
Nora Hosny ◽  
Anders W. Matson ◽  
Ramesh Kumbha ◽  
Magie Steinhoff ◽  
Joseph Sushil Rao ◽  
...  
Keyword(s):  
Cell Surface ◽  
Er Stress ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Signal Function

scholarly journals Obesity-Linked Variants of Melanocortin-4 Receptor Are Misfolded in the Endoplasmic Reticulum and Can Be Rescued to the Cell Surface by a Chemical Chaperone

2010 ◽  
Vol 31 (4) ◽  
pp. 605-605
Author(s):  
Susana Granell ◽  
Sameer Mohammad ◽  
Ramanagouda Ramanagoudr-Bhojappa ◽  
Giulia Baldini
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Er Stress ◽  
Binding Protein ◽  
Intracellular Localization ◽  
Specific Inhibitor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Chemical Chaperone ◽  
Melanocortin 4 Receptor

Abstract Melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in the brain where it controls food intake. Many obesity-linked MC4R variants are poorly expressed at the plasma membrane and are retained intracellularly. We have studied the intracellular localization of four obesity-linked MC4R variants, P78L, R165W, I316S, and I317T, in immortalized neurons. We find that these variants are all retained in the endoplasmic reticulum (ER), are ubiquitinated to a greater extent than the wild-type (wt) receptor, and induce ER stress with increased levels of ER chaperones as compared with wt-MC4R and appearance of CCAAT/enhancer-binding protein homologous protein. Expression of the X-box-binding-protein-1 with selective activation of a protective branch of the unfolded protein response did not have any effect on the cell surface expression of MC4R-I316S. Conversely, the pharmacological chaperone 4-phenyl butyric acid (PBA) increased the cell surface expression of wt-MC4R, MC4R-I316S, and I317T by more than 40%. PBA decreased ubiquitination of MC4R-I316S and prevented ER stress induced by expression of the mutant, suggesting that the drug functions to promote MC4R folding. MC4R-I316S rescued to the cell surface is functional, with a 52% increase in agonist-induced cAMP production, as compared with untreated cells. Also direct inhibition of wt-MC4R and MC4R-I316S ubiquitination by a specific inhibitor of the ubiquitin-activating enzyme 1 increased by approximately 40% the expression of the receptors at the cell surface, and the effects of PBA and ubiquitin-activating enzyme 1 were additive. These data offer a cell-based rationale that drugs that improve MC4R folding or decrease ER-associated degradation of the receptor may function to treat some forms of hereditary obesity.

scholarly journals ER Stress and Iron Homeostasis: A New Frontier for the UPR

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Susana J. Oliveira ◽  
Maria de Sousa ◽  
Jorge P. Pinto
Keyword(s):  
Cell Surface ◽  
Er Stress ◽  
Conformational Changes ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Clinical Value ◽  
Mhc I ◽  
Functional Perspective

The C282Y mutation of HFE accounts for the majority of cases of the iron overload disease Hereditary Hemochromatosis (HH). The conformational changes introduced by this mutation impair the HFE association with β2-microglobulin (β2m) and the cell surface expression of the protein: with two major consequences. From a functional perspective, the ability of HFE to bind to transferrin receptors 1 and 2 is lost in the C282Y mutant, thus affecting hepcidin regulation. Also due to the faulty assembly with β2m, HFE-C282Y molecules remain in the endoplasmic reticulum (ER) as aggregates that undergo proteasomal degradation and activate an Unfolded Protein Response (UPR). UPR activation, regardless of the ER stress stimuli, was shown to reshape the expression profile of iron-related genes and to decrease MHC-I cell surface expression. The possibility of a HFE-C282Y-mediated interplay between the UPR and iron homeostasis influencing disease progression and the clinical heterogeneity among C282Y carriers is discussed. The responsiveness of the ER chaperone calreticulin to both ER and iron-induced oxidative stresses, and its correlation with HH patients’ phenotype, reinforce the interest of dissecting the UPR signaling/iron metabolism crosstalk and points to the potential clinical value of use of pharmacological chaperones in HFE-HH.

Persistent HIV Transcription Induces Sialyl-Lewis-X Glyco-Antigen Cell-Surface Expression

2020 ◽  
Author(s):  
Florent Colomb ◽  
Leila B. Giron ◽  
Leticia Kuri Cervantes ◽  
Tongcui Ma ◽  
Samson Adeniji ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Sialyl Lewis X ◽  
Cell Surface Expression ◽  
Lewis X ◽  
Hiv Transcription ◽  
Sialyl Lewis

Influence of β-D-mannuronic acid, as a new member of non-steroidal anti-inflammatory drugs family, on expression pattern of chemokines and their receptors in rheumatoid arthritis

2019 ◽  
Vol 16 ◽  
Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mrna Expression ◽  
Surface Expression ◽  
Phase Iii ◽  
Cell Surface Expression ◽  
Optimum Dose ◽  
High Dose ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
High Doses

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

The immunogenicity of VP7, a rotavirus antigen resident in the endoplasmic reticulum, is enhanced by cell surface expression.

1990 ◽  
Vol 64 (10) ◽  
pp. 4776-4783 ◽  
Author(s):  
M E Andrew ◽  
D B Boyle ◽  
P L Whitfeld ◽  
L J Lockett ◽  
I D Anthony ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression
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