DER7, encoding $alpha;-glucosidase I is essential for degradation of malfolded glycoproteins of the endoplasmic reticulum

Hitt, Reiner

doi:10.1016/s1567-1356(04)00050-9

Cited by 11 publications

(16 citation statements)

References 13 publications

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“…The analysis of C. albicans genome databank identified two DNA fragments as the 5Ј and 3Ј ends of CaCWH41 (GenBank accession XM_718516 and XM_705221, respec- (29,31,77).…”

Section: Resultsmentioning

confidence: 99%

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Endoplasmic Reticulum α-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction

et al. 2007

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The cell surface of Candida albicans is enriched in highly glycosylated mannoproteins that are involved in the interaction with the host tissues. N glycosylation is a posttranslational modification that is initiated in the endoplasmic reticulum (ER), where the Glc 3 Man 9 GlcNAc 2 N-glycan is processed by ␣-glucosidases I and II and ␣1,2-mannosidase to generate Man 8 GlcNAc 2 . This N-oligosaccharide is then elaborated in the Golgi to form N-glycans with highly branched outer chains rich in mannose. In Saccharomyces cerevisiae, CWH41, ROT2, and MNS1 encode for ␣-glucosidase I, ␣-glucosidase II catalytic subunit, and ␣1,2-mannosidase, respectively. We disrupted the C. albicans CWH41, ROT2, and MNS1 homologs to determine the importance of N-oligosaccharide processing on the N-glycan outer-chain elongation and the host-fungus interaction. Yeast cells of Cacwh41⌬, Carot2⌬, and Camns1⌬ null mutants tended to aggregate, displayed reduced growth rates, had a lower content of cell wall phosphomannan and other changes in cell wall composition, underglycosylated ␤-N-acetylhexosaminidase, and had a constitutively activated PKC-Mkc1 cell wall integrity pathway. They were also attenuated in virulence in a murine model of systemic infection and stimulated an altered pro-and anti-inflammatory cytokine profile from human monocytes. Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions.Candida albicans is an opportunistic fungal pathogen of humans that can cause superficial infections of the mucosa and, in the immunocompromised host, life-threatening systemic infections (10,52,53,61). The cell wall of C. albicans is the immediate point of contact between the fungus and host and therefore plays a key role in the host-fungus interaction. The cell wall is composed of an inner layer of chitin and ␤1,3-and ␤1,6-glucans and an outer layer that is rich in mannoproteins that accounts for 40% of the yeast form cell wall mass (39).

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“…The analysis of C. albicans genome databank identified two DNA fragments as the 5Ј and 3Ј ends of CaCWH41 (GenBank accession XM_718516 and XM_705221, respec- (29,31,77).…”

Section: Resultsmentioning

confidence: 99%

“…It has been suggested that removal of this unique mannose residue induces a conformational reorganization in the N-glycan core that is required for the outer-chain synthesis (8). The core-processing ␣-glycosidases are also important for glycoprotein folding and for the ER quality control during glycoprotein biosynthesis (24,29).…”

mentioning

confidence: 99%

Endoplasmic Reticulum α-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction

et al. 2007

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“…Um-11723 showed significant similarity to the ER glucosidase I from S. cerevisiae and Candida albicans (Sc-Cwh41 and Ca-Cwh41, respectively). The U. maydis 11723 N-terminal domain includes the conserved amino acids sequence 652 Glu-Leu-His-Val-Asp-Leu 657 , which has been linked to substrate binding (Romaniouk and Vijay, 1997), and the critical residues Arg-502 and Gly-834 required for its full catalytic activity (Völker et al, 2002;Hitt and Wolf, 2004;Hong et al, 2004). We also identified Um-12045 as a putative homolog of the S. cerevisiae glucosidase II b-subunit (Gtb1).…”

Section: N-glycoprotein Glycan Trimming In U Maydismentioning

confidence: 97%

Endoplasmic Reticulum Glucosidases and Protein Quality Control Factors Cooperate to Establish Biotrophy inUstilago maydis

et al. 2013

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Secreted fungal effectors mediate plant-fungus pathogenic interactions. These proteins are typically N-glycosylated, a common posttranslational modification affecting their location and function. N-glycosylation consists of the addition, and subsequent maturation, of an oligosaccharide core in the endoplasmic reticulum (ER) and Golgi apparatus. In this article, we show that two enzymes catalyzing specific stages of this pathway in maize smut (Ustilago maydis), glucosidase I (Gls1) and glucosidase II b-subunit (Gas2), are essential for its pathogenic interaction with maize (Zea mays). Gls1 is required for the initial stages of infection following appressorium penetration, and Gas2 is required for efficient fungal spreading inside infected tissues. While U. maydis Dgls1 cells induce strong plant defense responses, Dgas2 hyphae are able to repress them, showing that slight differences in the N-glycoprotein processing can determine the extent of plant-fungus interactions. Interestingly, the calnexin protein, a central element of the ER quality control system for N-glycoproteins in eukaryotic cells, is essential for avoiding plant defense responses in cells with defective N-glycoproteins processing. Thus, N-glycoprotein maturation and this conserved checkpoint appear to play an important role in the establishment of an initial biotrophic state with the plant, which allows subsequent colonization.

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“…To summarize some of them, 1) calreticulin is absent from S. cerevisiae and calnexin lacks a cytosolic tail; therefore, it is unable to directly interact with cytosolic components. 2) Calnexin (250) and glucose trimming (157,175) are required for ERAD in lower eu-karyotes, whilst in mammalian cells, both calnexin and calreticulin are dispensable for ERAD and substrate association with them actually delays disposal. Moreover, it is undisputed that inhibition of glucose removal that results in a bypass of the calnexin cycle substantially accelerates onset of protein degradation in mammalian cells (14,52,69,139,191,192,264,270).…”

Section: Erad In Yeast Compared With Higher Eukaryotesmentioning

confidence: 99%

In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases

Hebert¹,

Molinari²

2007

Physiological Reviews

573

559

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A substantial fraction of eukaryotic gene products are synthesized by ribosomes attached at the cytosolic face of the endoplasmic reticulum (ER) membrane. These polypeptides enter cotranslationally in the ER lumen, which contains resident molecular chaperones and folding factors that assist their maturation. Native proteins are released from the ER lumen and are transported through the secretory pathway to their final intra- or extracellular destination. Folding-defective polypeptides are exported across the ER membrane into the cytosol and destroyed. Cellular and organismal homeostasis relies on a balanced activity of the ER folding, quality control, and degradation machineries as shown by the dozens of human diseases related to defective maturation or disposal of individual polypeptides generated in the ER.

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DER7, encoding $alpha;-glucosidase I is essential for degradation of malfolded glycoproteins of the endoplasmic reticulum

Cited by 11 publications

References 13 publications

Endoplasmic Reticulum α-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction

Endoplasmic Reticulum α-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction

Endoplasmic Reticulum Glucosidases and Protein Quality Control Factors Cooperate to Establish Biotrophy inUstilago maydis

In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases

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