scholarly journals Endoplasmic Reticulum Glycoprotein Quality Control Regulates CD1d Assembly and CD1d-mediated Antigen Presentation

2013 ◽  
Vol 288 (23) ◽  
pp. 16391-16402 ◽  
Author(s):  
Amit Kunte ◽  
Wei Zhang ◽  
Crina Paduraru ◽  
Natacha Veerapen ◽  
Liam R. Cox ◽  
...  

The non-classical major histocompatibility complex (MHC) homologue CD1d presents lipid antigens to innate-like lymphocytes called natural-killer T (NKT) cells. These cells, by virtue of their broad cytokine repertoire, shape innate and adaptive immune responses. Here, we have assessed the role of endoplasmic reticulum glycoprotein quality control in CD1d assembly and function, specifically the role of a key component of the quality control machinery, the enzyme UDP glucose glycoprotein glucosyltransferase (UGT1). We observe that in UGT1-deficient cells, CD1d associates prematurely with β2-microglobulin (β2m) and is able to rapidly exit the endoplasmic reticulum. At least some of these CD1d-β2m heterodimers are shorter-lived and can be rescued by provision of a defined exogenous antigen, α-galactosylceramide. Importantly, we show that in UGT1-deficient cells the CD1d-β2m heterodimers have altered antigenicity despite the fact that their cell surface levels are unchanged. We propose that UGT1 serves as a quality control checkpoint during CD1d assembly and further suggest that UGT1-mediated quality control can shape the lipid repertoire of newly synthesized CD1d. The quality control process may play a role in ensuring stability of exported CD1d-β2m complexes, in facilitating presentation of low abundance high affinity antigens, or in preventing deleterious responses to self lipids.

2012 ◽  
Vol 263-266 ◽  
pp. 839-842 ◽  
Author(s):  
Zhong Qiu Jiang

SPC (statistical process control) and EPC (engineering process control) is the scientific methods of quality quality control and quality improvement. It is the difficult problems of quality control process for network manufacturing enterprise how to effectively solve the dynamic quality fluctuation monitoring and the fluctuation abnormal diagnostic analysis and timely process adjustments, this paper designs the intelligent quality control mode and function system architecture, the modes expatiates quality management network based on quality control network of the workshop level and enterprise class network, and researches the integration applications of statistical process control and enterprise ERP quality system, and applies J2EE technology to achieve the system organic combination of design and development.


2011 ◽  
Vol 22 (19) ◽  
pp. 3559-3570 ◽  
Author(s):  
Yang Chen ◽  
Dan Hu ◽  
Rikio Yabe ◽  
Hiroaki Tateno ◽  
Sheng-Ying Qin ◽  
...  

Malectin was first discovered as a novel endoplasmic reticulum (ER)–resident lectin from Xenopus laevis that exhibits structural similarity to bacterial glycosylhydrolases. Like other intracellular lectins involved in glycoprotein quality control, malectin is highly conserved in animals. Here results from in vitro membrane-based binding assays and frontal affinity chromatography confirm that human malectin binds specifically to Glc2Man9GlcNAc2 (G2M9) N-glycan, with a Ka of 1.97 × 105 M−1, whereas binding to Glc1Man9GlcNAc2 (G1M9), Glc3Man9GlcNAc2 (G3M9), and other N-glycans is barely detectable. Metabolic labeling and immunoprecipitation experiments demonstrate that before entering the calnexin cycle, the folding-defective human α1-antitrypsin variant null Hong Kong (ATNHK) stably associates with malectin, whereas wild-type α1-antitrypsin (AT) or N-glycan–truncated variant of ATNHK (ATNHK-Q3) dose not. Moreover, malectin overexpression dramatically inhibits the secretion of ATNHK through a mechanism that involves enhanced ER-associated protein degradation; by comparison, the secretion of AT and ATNHK-Q3 is only slightly affected by malectin overexpression. ER-stress induced by tunicamycin results in significantly elevated mRNA transcription of malectin. These observations suggest a possible role of malectin in regulating newly synthesized glycoproteins via G2M9 recognition.


2019 ◽  
Author(s):  
Aeid Igbaria ◽  
Philip I. Merksamer ◽  
Ala Trusina ◽  
Firehiwot Tilahun ◽  
Jefferey R. Johnson ◽  
...  

ABSTRACTDiverse perturbations to endoplasmic reticulum (ER) functions compromise the proper folding and structural maturation of secretory proteins. To study secretory pathway physiology during such “ER stress”, we employed an ER-targeted, redox-responsive, green fluorescent protein—eroGFP—that reports on ambient changes in oxidizing potential. Here we find that diverse ER stress agents cause properly folded, ER-resident eroGFP (and other ER luminal proteins) to “reflux” back to the reducing environment of the cytosol as intact, folded proteins. By utilizing eroGFP in a comprehensive genetic screen in S. cerevisiae, we show that ER protein reflux during ER stress requires specific chaperones and co-chaperones residing in both the ER and the cytosol. Chaperone-mediated ER protein reflux does not require E3 ligase activity, and proceeds even more vigorously when these ER-associated degradation (ERAD) factors are crippled, suggesting that reflux may work in parallel with ERAD. In summary, chaperone-mediated ER-protein reflux may be a conserved protein quality control process that evolved to maintain secretory pathway homeostasis during ER protein-folding stress.SIGNIFICANCEApproximately one third of eukaryotic proteins are synthesized on ribosomes attached to the endoplasmic reticulum (ER) membrane. Many of these polypeptides co- or post-translationally translocate into the ER, wherein they fold and mature. An ER quality-control system proofreads these proteins by facilitating their folding and modification, while eliminating misfolded proteins through ER-associated degradation (ERAD). Yet, the fate of many secretory proteins during ER stress is not completely understood. Here, we uncovered an ER-stress induced “protein reflux” system that delivers intact, folded ER luminal proteins back to the cytosol without degrading them. We found that ER protein reflux works in parallel to ERAD and requires distinct ER-resident and cytosolic chaperones and co-chaperones.


Author(s):  
M. Ivey ◽  
Y. Mohamed ◽  
P. Musilek ◽  
D. Raboud ◽  
A. Rajendran ◽  
...  

The importance of a good syllabus as part of delivering a course is well known. However, it is an all too often a reality that syllabi are prepared hastily, inconsistent from program expectations and missing vital information. The primary role of the syllabus is to help instructors prepare and deliver the expected course content to students. However, it can also be used as a tool to aid programs in their continual improvement and quality control process. Further, it can be used to automatically collect vital information for accreditation purposes.In this paper, we introduce a Syllabus Assembly and Management System (SAMS) that supports our instructors and our programs teaching mandate


2021 ◽  
Vol 17 (2) ◽  
pp. e1008654
Author(s):  
Aidan I. Brown ◽  
Elena F. Koslover

Newly-translated glycoproteins in the endoplasmic reticulum (ER) often undergo cycles of chaperone binding and release in order to assist in folding. Quality control is required to distinguish between proteins that have completed native folding, those that have yet to fold, and those that have misfolded. Using quantitative modeling, we explore how the design of the quality-control pathway modulates its efficiency. Our results show that an energy-consuming cyclic quality-control process, similar to the observed physiological system, outperforms alternative designs. The kinetic parameters that optimize the performance of this system drastically change with protein production levels, while remaining relatively insensitive to the protein folding rate. Adjusting only the degradation rate, while fixing other parameters, allows the pathway to adapt across a range of protein production levels, aligning with in vivo measurements that implicate the release of degradation-associated enzymes as a rapid-response system for perturbations in protein homeostasis. The quantitative models developed here elucidate design principles for effective glycoprotein quality control in the ER, improving our mechanistic understanding of a system crucial to maintaining cellular health.


2021 ◽  
pp. 1-11
Author(s):  
Song Gang ◽  
Wang Xiaoming ◽  
Wu Junfeng ◽  
Li Shufang ◽  
Liu Zhuowen ◽  
...  

In view of the production quality management of filter rods in the manufacturing and execution process of cigarette enterprises, this paper analyzes the necessity of implementing the manufacturing execution system (MES) in the production process of filter rods. In this paper, the filter rod quality system of cigarette enterprise based on MES is fully studied, and the constructive information management system demand analysis, cigarette quality control process, system function module design, implementation and test effect are given. This paper utilizes the Fuzzy analytic hierarchy process to find the optimal system for processing the manufacturing of cigarette. The implementation of MSE based filter rod quality information management system for a cigarette enterprise ensures the quality control in the cigarette production process. Through visualization, real-time and dynamic way, the information management of cigarette production is completed, which greatly improves the quality of cigarette enterprise manufacturing process.


Cell ◽  
2021 ◽  
Vol 184 (11) ◽  
pp. 2896-2910.e13
Author(s):  
Haifeng Jiao ◽  
Dong Jiang ◽  
Xiaoyu Hu ◽  
Wanqing Du ◽  
Liangliang Ji ◽  
...  

2013 ◽  
Vol 141 (2) ◽  
pp. 798-808 ◽  
Author(s):  
Zhifang Xu ◽  
Yi Wang ◽  
Guangzhou Fan

Abstract The relatively smooth terrain embedded in the numerical model creates an elevation difference against the actual terrain, which in turn makes the quality control of 2-m temperature difficult when forecast or analysis fields are utilized in the process. In this paper, a two-stage quality control method is proposed to address the quality control of 2-m temperature, using biweight means and a progressive EOF analysis. The study is made to improve the quality control of the observed 2-m temperature collected by China and its neighboring areas, based on the 6-h T639 analysis from December 2009 to February 2010. Results show that the proposed two-stage quality control method can secure the needed quality control better, compared with a regular EOF quality control process. The new method is, in particular, able to remove the data that are dotted with consecutive errors but showing small fluctuations. Meanwhile, compared with the lapse rate of temperature method, the biweight mean method is able to remove the systematic bias generated by the model. It turns out that such methods make the distributions of observation increments (the difference between observation and background) more Gaussian-like, which ensures the data quality after the quality control.


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