Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder

Gallo, Giovanna; Valko, Ayelén; Aramburu, Sofía Ivana; Etchegaray, Emiliana; Völker, Christof; Parodi, Armando J.; D’Alessio, Cecilia

doi:10.1074/jbc.ra118.004844

Cited by 9 publications

(9 citation statements)

References 44 publications

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“…ER α-glucosidase I (GCS1, in purple on the left-hand side in Figure 1) directly interacts with subunits of the ER-membrane-associated oligosaccharyl transferase (OST) [30, 31], in agreement with what was observed for the yeast orthologues [32, 33]. GCS1 acts as the porter at the ERQC one-way entrance door, removing the outer glucose (Glc) residue from the Glc 3 Man 9 GlcNAc 2 N-linked glycan transferred by OST to a nascent glycoprotein.…”

Section: Methodssupporting

confidence: 69%

“…With this cleavage, ER Glu I generates diglucosylated glycoproteins, i.e., glycoproteins carrying Glc 2 Man 9 GlcNAc 2 N-linked glycans. This kind of glycan in turn is necessary for the first interaction with the second major ERQC player, ER α Glu II: without the ER α Glu I-mediated Glc cleavage, glycoproteins cannot interact with ER α Glu II nor enter ERQC [32, 33]. A direct role for diglucosylated glycans in ERQC has also been hypothesised in conjunction with malectin, the ER lectin that binds them specifically [34].…”

Section: Methodsmentioning

confidence: 99%

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Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?

Tax

Lia

Santino

et al. 2019

Journal of Oncology

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Endoplasmic reticulum glycoprotein folding quality control (ERQC) and ER-associated degradation (ERAD) preside over cellular glycoprotein secretion and maintain steady glycoproteostasis. When cells turn malignant, cancer cell plasticity is affected and supported either by point mutations, preferential isoform selection, altered expression levels, or shifts to conformational equilibria of a secreted glycoprotein. Such changes are crucial in mediating altered extracellular signalling, metabolic behavior, and adhesion properties of cancer cells. It is therefore conceivable that interference with ERQC and/or ERAD can be used to selectively damage cancers. Indeed, inhibitors of the late stages of ERAD are already in the clinic against cancers such as multiple myeloma. Here, we review recent advances in our understanding of the complex relationship between glycoproteostasis and cancer biology and discuss the potential of ERQC and ERAD modulators for the selective targeting of cancer cell plasticity.

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Section: Methodssupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?

Tax

Lia

Santino

et al. 2019

Journal of Oncology

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“…The high conservation of sequence and function of ERQC components across eukaryotes makes it possible to use fungi and plants for basic studies of ERQC in cellula [19] and in vivo [20], respectively, without the ethical and economical complications of mammalian animal models. Any phenotype mediated by glycoproteins whose folding is controlled by ERQC enables the study of ERQC function in vivo.…”

Section: Introductionmentioning

confidence: 99%

EFR-Mediated Innate Immune Response in Arabidopsis thaliana is a Useful Tool for Identification of Novel ERQC Modulators

Lia

Gallo

Marti

et al. 2018

Genes

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Plants offer a simpler and cheaper alternative to mammalian animal models for the study of endoplasmic reticulum glycoprotein folding quality control (ERQC). In particular, the Arabidopsis thaliana (At) innate immune response to bacterial peptides provides an easy means of assaying ERQC function in vivo. A number of mutants that are useful to study ERQC in planta have been described in the literature, but only for a subset of these mutants the innate immune response to bacterial elicitors has been measured beyond monitoring plant weight and some physio-pathological parameters related to the plant immune response. In order to probe deeper into the role of ERQC in the plant immune response, we monitored expression levels of the Phosphate-induced 1 (PHI-1) and reticulin-oxidase homologue (RET-OX) genes in the At ER α-Glu II rsw3 and the At UGGT uggt1-1 mutant plants, in response to bacterial peptides elf18 and flg22. The elf18 response was impaired in the rsw3 but not completely abrogated in the uggt1-1 mutant plants, raising the possibility that the latter enzyme is partly dispensable for EF-Tu receptor (EFR) signaling. In the rsw3 mutant, seedling growth was impaired only by concomitant application of the At ER α-Glu II NB-DNJ inhibitor at concentrations above 500 nM, compatibly with residual activity in this mutant. The study highlights the need for extending plant innate immune response studies to assays sampling EFR signaling at the molecular level.

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“…Chaperones such as DNAJA1 and CRYAA play a crucial role in marking aberrant proteins for ER-associated degradation (ERAD) ( Shen et al., 2002 ). Proteomic scrutiny of pt55_7 strains under grazing pressures, accentuated the up-regulation of GANAB, facilitating deglycosylation processes ( Gallo et al., 2018 ), and ERManI, responsible for mannose glycol-groups cleavage ( Maki et al., 2022 ). The increased of HSP110 activity further substantiates the role of heat proteins in ER-associated degradation ( Hrizo et al., 2007 ), while a decline in SKP1 activity implies attenuated proteasomal ubiquitination ( Yoshida and Tanaka, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-omic insights into the cellular response of Phaeodactylum tricornutum (Bacillariophyta) strains under grazing pressure

Liu,

Li,

Yang

et al. 2024

Front. Plant Sci.

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Background/AimsPhaeodactylum tricornutum, a model organism of diatoms, plays a crucial role in Earth’s primary productivity. Investigating its cellular response to grazing pressure is highly significant for the marine ecological environment. Furthermore, the integration of multi-omics approaches has enhanced the understanding of its response mechanism.MethodsTo assess the molecular and cellular responses of P.tricornutum to grazer presence, we conducted transcriptomic, proteomic, and metabolomic analyses, combined with phenotypic data from previous studies. Sequencing data were obtained by Illumina RNA sequencing, TMT Labeled Quantitative Proteomics and Non-targeted Metabolomics, and WGCNA analysis and statistical analysis were performed.ResultsAmong the differentially expressed genes, we observed complex expression patterns of the core genes involved in the phenotypic changes of P.tricornutum under grazing pressure across different strains and multi-omics datasets. These core genes primarily regulate the levels of various proteins and fatty acids, as well as the cellular response to diverse signals.ConclusionOur research reveals the association of multi-omics in four strains responses to grazing effects in P.tricornutum. Grazing pressure significantly impacted cell growth, fatty acid composition, stress response, and the core genes involved in phenotype transformation.

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Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder

Abstract: The authors declare that they have no conflicts of interest with the contents of this article. This article contains Figs. S1-S5 and Table S1.

Cited by 9 publications

References 44 publications

Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?

Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?

EFR-Mediated Innate Immune Response in Arabidopsis thaliana is a Useful Tool for Identification of Novel ERQC Modulators

Multi-omic insights into the cellular response of Phaeodactylum tricornutum (Bacillariophyta) strains under grazing pressure

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