Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex

Tian, Songhai; Wu, Qiulian; Zhou, Bo; Choi, Mei Yuk; Ding, Bo; Yang, Wei; Dong, Min

doi:10.1016/j.celrep.2019.08.006

Cited by 55 publications

(91 citation statements)

References 34 publications

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“…significantly depleted in EMC2-or EMC4-deficient cells, even though translation rates remained effectively unchanged (Shurtleff et al, 2018). In yeast, profiles of translating ribosomes proximal to EMC5 revealed enrichment of polytopic membrane proteins with 'atypical' TMDs that contain charged residues, including a number of members belonging to the solute carrier (SLC) family of membrane transport proteins, such as SLC43A3 (Shurtleff et al, 2018;Tian et al, 2019). Quantitative proteomic methodologies have been powerful predictors of EMC-dependent client proteins by monitoring changes in their abundance within EMC-deficient cells (Shurtleff et al, 2018;Volkmar et al, 2019).…”

Section: Emc-dependent Clientsmentioning

confidence: 99%

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Volkmar

Christianson

2020

Journal of Cell Science

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Integral membrane proteins play key functional roles at organelles and the plasma membrane, necessitating their efficient and accurate biogenesis to ensure appropriate targeting and activity. The endoplasmic reticulum membrane protein complex (EMC) has recently emerged as an important eukaryotic complex for biogenesis of integral membrane proteins by promoting insertion and stability of atypical and sub-optimal transmembrane domains (TMDs). Although confirmed as a bona fide complex almost a decade ago, light is just now being shed on the mechanism and selectivity underlying the cellular responsibilities of the EMC. In this Review, we revisit the myriad of functions attributed the EMC through the lens of these new mechanistic insights, to address questions of the cellular and organismal roles the EMC has evolved to undertake.

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Section: Emc-dependent Clientsmentioning

confidence: 99%

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Volkmar

Christianson

2020

Journal of Cell Science

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“…To explore the molecular mechanisms involved in the two adjuvants, tandem mass tags (TMT) technology was used for quantitative proteomic analysis according to previously described method [39,40]. Serum (0.5 mL) was prepared from each animal and pooled in the same group, which was then divided into three samples used for the test.…”

Section: Proteomic Analysismentioning

confidence: 99%

Enhanced Immune Responses with Serum Proteomic Analysis of Hu Sheep to Foot-and-Mouth Disease Vaccine Emulsified in a Vegetable Oil Adjuvant

et al. 2020

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Our previous study demonstrated that a vegetable oil consisting of soybean oil, vitamin E, and ginseng saponins (SO-VE-GS) had an adjuvant effect on a foot-and-mouth disease (FMD) vaccine in a mouse model. The present study was to compare the adjuvant effects of SO-VE-GS and the conventional ISA 206 on an FMD vaccine in Hu sheep. Animals were intramuscularly (i.m.) immunized twice at a 3-week interval with 1 mL of an FMD vaccine adjuvanted with SO-VE-GS (n = 10) or ISA 206 (n = 9). Animals without immunization served as control (n = 10). Blood was sampled prior to vaccination and at 2, 4, 6, and 8 weeks post the booster immunization to detect FMD virus (FMDV)-specific IgG. Blood collected at 8 weeks after the booster was used for the analyses of IgG1 and IgG2, serum neutralizing (SN) antibody, IL-4 and IFN-γ production, and proteomic profiles. The results showed that IgG titers rose above the protection level (1:128) in SO-VE-GS and ISA 206 groups after 2 and 4 weeks post the booster immunization. At 6 weeks post the booster, the ISA 206 group had 1 animal with IgG titer less than 1:128 while all the animals in the SO-VE-GS group retained IgG titers of more than 1:128. At 8 weeks post the booster, 6 of 9 animals had IgG titers less than 1:128 with a protective rate of 33.3% in the ISA 206 group, while only 1 of 10 animals had IgG titer less than 1:128 with a protective rate of 90% in the SO-VE-GS group, with statistical significance. In addition, IgG1, IgG2, SN antibodies, IL-4, and IFN-γ in the SO-VE-GS group were significantly higher than those of the ISA 206 group. Different adjuvant effects of SO-VE-GS and ISA 206 may be explained by the different proteomic profiles in the two groups. There were 39 and 47 differentially expressed proteins (DEPs) identified in SO-VE-GS compared to the control or ISA 206 groups, respectively. In SO-VE-GS vs. control, 3 immune related gene ontology (GO) terms and 8 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were detected, while 2 immune related GO terms and 5 KEGG pathways were found in ISA 206 vs. control. GO and KEGG analyses indicated that ‘positive regulation of cytokine secretion’, ‘Th1/Th2 cell differentiation’, and ‘Toll-like receptor signaling pathways’, were obviously enriched in the SO-VE-GS group compared to the other groups. Coupled with protein–protein interaction (PPI) analysis, we found that B7TJ15 (MAPK14) was a key DEP for SO-VE-GS to activate the immune responses in Hu sheep. Therefore, SO-VE-GS might be a promising adjuvant for an FMD vaccine in Hu sheep.

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“…Loss of the EMC in mammalian cells is associated with failed biogenesis and degradation of a subset of membrane proteins ( Christianson et al, 2012 ). Accordingly, the EMC has been implicated in several mechanistically distinct steps of membrane protein biogenesis, stabilization, and quality control ( Bircham et al, 2011 ; Richard et al, 2013 ; Satoh et al, 2015 ; Savidis et al, 2016 ; Shurtleff et al, 2018 ; Volkmar et al, 2019 ; Tian et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients

Miller-Vedam

Bräuning

Popova

et al. 2020

eLife

111

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Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two lipid-accessible membrane cavities which confer client-specific regulation, and a non-insertase EMC function mediated by the EMC lumenal domain. Our studies illuminate the structural and mechanistic basis of EMC's multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes.

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Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex

Cited by 55 publications

References 34 publications

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Enhanced Immune Responses with Serum Proteomic Analysis of Hu Sheep to Foot-and-Mouth Disease Vaccine Emulsified in a Vegetable Oil Adjuvant

Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients

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