Htm1p, a mannosidase‐like protein, is involved in glycoprotein degradation in yeast

Jakob, Claude A.; Bodmer, Daniel; Spirig, Urs; Bättig, Patrick; Marcil, Anne; Dignard, Daniel; Bergeron, John J.M.; Thomas, David Y.; Aebi, Markus

doi:10.1093/embo-reports/kve089

Cited by 236 publications

(181 citation statements)

References 40 publications

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“…One pool comprised structures ( Fig. 2A, top, peaks a-e) that were sensitive to an amyloglucosidase preparation from Rhizopus mold 3 and occurred in png1⌬ ( Fig. 2A, top, red trace) and ams1⌬ ( Fig.…”

Section: Png1p-dependent Fos Are Regulated During Post-diauxic Growthmentioning

confidence: 99%

Endoplasmic Reticulum-associated Degradation (ERAD) and Free Oligosaccharide Generation in Saccharomyces cerevisiae

Chantret

Kodali

Lahmouich

et al. 2011

Journal of Biological Chemistry

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Background: Yeast free oligosaccharides (fOS) are cleaved from glycoproteins during ER-associated degradation of proteins (ERAD), but factors underlying their control remain to be explored. Results: Only one-half of fOS are regulated by known ERAD processes, and fOS generation and demannosylation are growth-dependent. Conclusion: Additional complexity of ERAD processes is revealed. Significance: This is the first demonstration of growth-dependent fOS regulation.

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Section: Png1p-dependent Fos Are Regulated During Post-diauxic Growthmentioning

confidence: 99%

Endoplasmic Reticulum-associated Degradation (ERAD) and Free Oligosaccharide Generation in Saccharomyces cerevisiae

Chantret

Kodali

Lahmouich

et al. 2011

Journal of Biological Chemistry

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“…CHX chase experiments were performed as described previously (Plemper et al, 1998;Jakob et al, 2001). Briefly, overnight cultures were inoculated into 5 ml of medium.…”

Section: Cycloheximide (Chx) Chase Analysismentioning

confidence: 99%

“…Therefore, we next examined whether the lowered steady-state level of Gas1*p is because of a rapid degradation of misfolded protein. A CHX chase experiment (Plemper et al, 1998;Jakob et al, 2001) showed that Gas1*p was present initially as the ER form but rapidly decreased to an undetectable level, whereas wild-type Gas1p and the control ER marker Dpm1p were stable even after protein synthesis was stopped by CHX ( Figure 4A). In addition, in the CHX chase experiment, Gas1*p remained as the ER form but showed a gradually increased molecular weight.…”

Section: Construction and Characterization Of Misfolded Gas1mentioning

confidence: 99%

“…We used mns1⌬ and htm1⌬ mutants to determine whether the quality control mechanisms of glycoproteins are involved in the degradation of misfolded GPI-anchored proteins. MNS1 is required for the mannose trimming of an oligosaccharide (Camirand et al, 1991), and HTM1 is involved in the recognition of the oligosaccharide portion of misfolded glycoproteins (Jakob et al, 2001). The degradation of misfolded glycoproteins was stabilized in these mutants.…”

Section: Degradation Of Gas1* Protein In Mutants Of Gpi Biosynthesismentioning

confidence: 99%

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Inositol Deacylation by Bst1p Is Required for the Quality Control of Glycosylphosphatidylinositol-anchored Proteins

Fujita

Yoko-o

Jigami

2006

MBoC

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Misfolded proteins are recognized in the endoplasmic reticulum (ER), transported back to the cytosol, and degraded by the proteasome. A number of proteins are processed and modified by a glycosylphosphatidylinositol (GPI) anchor in the ER, but the quality control mechanisms of GPI-anchored proteins remain unclear. Here, we report on the quality control mechanism of misfolded GPI-anchored proteins. We have constructed a mutant form of the ␤-1,3-glucanosyltransferase Gas1p (Gas1*p) as a model misfolded GPI-anchored protein. Gas1*p was modified with a GPI anchor but retained in the ER and was degraded rapidly via the proteasome. Disruption of BST1, which encodes GPI inositol deacylase, caused a delay in the degradation of Gas1*p. This delay was because of an effect on the deacylation activity of Bst1p. Disruption of genes involved in GPI-anchored protein concentration and N-glycan processing caused different effects on the degradation of Gas1*p and a soluble misfolded version of carboxypeptidase Y. Furthermore, Gas1*p associated with both Bst1p and BiP/Kar2p, a molecular chaperone, in vivo. Our data suggest that GPI inositol deacylation plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins. INTRODUCTIONCells possess several quality control mechanisms for the maintenance of proper protein folding and function. On synthesis, membrane and secretory proteins are inserted into the lumen of the endoplasmic reticulum (ER), where they are folded and undergo oligomerization. There are a number of chaperones and enzymes in the ER required for proper protein folding (Ellgaard et al., 1999). Before exiting from the ER, proteins are monitored by a quality control system that ensures correct folding. Misfolded proteins that fail to pass the quality control checkpoint are transported back to the cytosol and degraded by an ER-associated degradation (ERAD) mechanism that involves the ubiquitinproteasome pathway (Kopito, 1997;Kostova and Wolf, 2003). N-linked oligosaccharide, one of the major posttranslational modifications in the ER, is trimmed and processed by glucosidase I, glucosidase II, and mannosidase I (Jakob et al., 1998;Helenius and Aebi, 2001). The processing of Nlinked oligosaccharides plays important roles in the quality control of glycoprotein folding in the ER Aebi, 2001, 2004).A number of cell surface proteins are posttranslationally modified in the ER with glycosylphosphatidylinositol (GPI). Mechanisms for quality control and degradation of GPIanchored proteins are important in folding diseases, including prion diseases and transmissible spongiform encephalopathies, which are caused by a conformational modification of prion, a GPI-anchored protein (Prusiner, 1998). There have been several biochemical studies on both the degradation of mutated prions and the quality control of proteins with mutated GPI attachment signals (Field et al., 1994;Oda et al., 1996;Wainwright and Field, 1997;Jin et al., 2000;Ito et al., 2002;Ishida et al., 2003). In contrast, the molecular mech...

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“…A mannosidaselike protein Mnl1p recognizes a single isomer of Man 8 GlcNAc 2 glycan of misfolded glycoprotein, and cuts off a terminal 1,2-alpha-mannose residue from the C-chain to generate Man 7 GlcNAc 2 glycan (Figure 2 et Jakob et al, 2001;Nakatsukasa et al, 2001). Lectin Yos9p recognizes the generated 1,6-alpha-linked mannose terminal of Man 7 GlcNAc 2 glycan and then accelerates the ERAD (Buschhorn et al, 2004;Clerc et al, 2009;Friedmann et al, 2002;Gauss et al, 2006;Kanehara et al, 2007;Szathmary et al, 2005).…”

Section: Hm-1-resistant Phenotypes Of Mns1 Do Not Participate In Endomentioning

confidence: 99%

Genome‐wide screen of Saccharomyces cerevisiae for killer toxin HM‐1 resistance

Miyamoto

Furuichi

Komiyama

2010

Yeast

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We screened a set of Saccharomyces cerevisiae deletion mutants for resistance to killer toxin HM-1, which kills susceptible yeasts through inhibiting 1,3-beta-glucan synthase. By using HM-1 plate assay, we found that eight gene-deletion mutants had higher HM-1-resistance compared with the wild-type. Among these eight genes, five -ALG3, CAX4, MNS1, OST6 and YBL083C -were associated with N -glycan formation and maturation. The ALG3 gene has been shown before to be highly resistant to HM-1. The YBL083C gene may be a dubious open reading frame that overlaps partially the ALG3 gene. The deletion mutant of the MNS1 gene that encodes 1,2-alpha-mannosidase showed with a 13-fold higher HM-1 resistance compared with the wild-type. By HM-1 binding assay, the yeast plasma membrane fraction of alg3 and mns1 cells had less binding ability compared with wild-type cells. These results indicate that the presence of the terminal 1,3-alpha-linked mannose residue of the B-chain of the N -glycan structure is essential for interaction with HM-1. A deletion mutant of aquaglyceroporin Fps1p also showed increased HM-1 resistance. A deletion mutant of osmoregulatory mitogen-activated protein kinase Hog1p was more sensitive to HM-1, suggesting that high-osmolarity glycerol pathways plays an important role in the compensatory response to HM-1 action.

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Htm1p, a mannosidase‐like protein, is involved in glycoprotein degradation in yeast

Cited by 236 publications

References 40 publications

Endoplasmic Reticulum-associated Degradation (ERAD) and Free Oligosaccharide Generation in Saccharomyces cerevisiae

Endoplasmic Reticulum-associated Degradation (ERAD) and Free Oligosaccharide Generation in Saccharomyces cerevisiae

Inositol Deacylation by Bst1p Is Required for the Quality Control of Glycosylphosphatidylinositol-anchored Proteins

Genome‐wide screen of Saccharomyces cerevisiae for killer toxin HM‐1 resistance

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