Cytosol-to-lysosome Transport of Free Polymannose-type Oligosaccharides

Saint‐Pol, Agnès; Codogno, Patrice; Moore, Stuart

doi:10.1074/jbc.274.19.13547

Cited by 62 publications

(42 citation statements)

References 55 publications

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“…Currently, two glycosidases (endo-␤-N-acetylglucosaminidase (11) and Man2C1 (12)) are known to be involved in the catabolism of free, high mannose-type oligosaccharides in the cytosol of mammalian cells. The processing of free oligosaccharides by these enzymes is postulated to be important for the subsequent transport of the oligosaccharides into lysosomes by a putative oligosaccharide transporter on the lysosomal membrane (13); this hypothesis is consistent with the observation that down-regulation or inhibition of Man2C1 leads to oligosaccharide accumulation in the cytosol (12, 14 -17).…”

supporting

confidence: 73%

Dual Functions for Cytosolic α-Mannosidase (Man2C1)

Wang¹,

Suzuki²

2013

Journal of Biological Chemistry

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supporting

confidence: 73%

Dual Functions for Cytosolic α-Mannosidase (Man2C1)

Wang¹,

Suzuki²

2013

Journal of Biological Chemistry

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“…The fate of this oligosaccharide is still in question, because up to now, no ␣-glucosidase activity has been detected in the cytosol. Although its transport into lysosomes has not yet been studied (25), our results suggest a lysosomal degradation into Man 5 GlcNAc 1 and lower species. The question remains whether glycoproteins bearing monoglucosylated glycans and being directed toward degradation must be linked to calnexin, as demonstrated by Liu et al (26) for the degradation of misfolded ␣1-antitrypsin.…”

Section: Discussionmentioning

confidence: 74%

Monoglucosylated Oligomannosides Are Released during the Degradation Process of Newly Synthesized Glycoproteins

Cacan

Duvet

Labiau

et al. 2001

Journal of Biological Chemistry

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The Chinese hamster ovary mutant MI8 -5 is known to synthesize Man 9 GlcNAc 2 -P-P-dolichol rather than the fully glucosylated lipid intermediate Glc 3 Man 9 GlcNAc 2 -P-P-dolichol. This nonglucosylated oligosaccharide lipid precursor is used as donor for N-glycosylation. In this paper we demonstrate that a significant part of the glycans bound to the newly synthesized glycoproteins in MI8 -5 cells are monoglucosylated. The presence of monoglucosylated glycans on glycoproteins determines their binding to calnexin as part of the quality control machinery. Furthermore, we point out the presence of Glc 1 Man 5 GlcNAc 1 in the cytosol of MI8 -5 cells. This indicates that part of the monoglucosylated glycoproteins can be directed toward a deglycosylation process that occurs in the cytosol. Besides studies on glycoprotein degradation based on the disappearance of protein moieties, MI8 -5 cells can be used as a tool to elucidate the various step leading to glycoprotein degradation by studying the fate of the glycan moieties.A key reaction of N-glycosylation is the transfer en bloc of a Glc 3 Man 9 GlcNAc 2 oligosaccharide from a lipid intermediate to an Asn residue in the Asn-Xaa-Ser(Thr) consensus sequence of a nascent protein. This N-glycosylation process is immediately followed by sequential deglucosylation leading to Man 9 GlcNAc 2 protein. It is now clearly established that oligosaccharide trimming in the ER 1 is intimately linked to the quality control process, leading to the degradation of misfolded glycoproteins or unassembled multimeric proteins. Indeed the presence of monoglucosylated oligomannosides on glycoproteins retained in the ER is essential for their binding to the molecular chaperones calnexin and calreticulin (1, 2). The presence of a glucosyl residue is controlled by reglucosylation-deglucosylation cycles involving UDP-glucose : glycoprotein glucosyltransferase acting as a folding sensor (3) and glucosidase II, respectively. It has been demonstrated that glucose trimming and reglucosylation cycles determine the association of a glycoprotein with calnexin, as well as its folding (4,5).During this quality control, part of newly synthesized glycoproteins are degraded after translocation of the glycosylated polypeptide chains from the ER to the cytosol. As first demonstrated by Wiertz et al. (6), using labeled protein with an amino acid precursor, this retrotranslocation is accompanied by the removal of the glycans by a cytosolic peptide N-glycanase (PNGase), such as the one isolated by Suzuki et al. (7). The relationship between the location of the enzyme and the degradation process has been discussed by Karaivanova and Spiro (8). However, it is worth mentioning that few labs follow the fate of newly synthesized proteins by labeling with [2-3 H]mannose. In this case, the N-glycosylation process is accompanied by the release of glycans from either lipid intermediates or from newly synthesized glycoproteins (9 -11). The trafficking of the released oligomannosides from both origins leads to the formatio...

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“…Oligosaccharide transporters often have broad specificity with some selectivity toward particular types of sugars (Saint-Pol et al, 1999). Bacterial transporters able to take up both a-and b-galactosides are common, but bacterial galactoside transporters are reported not to take up Suc (Okazaki et al, 1997).…”

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confidence: 99%

Mrt, a Gene Unique to Fungi, Encodes an Oligosaccharide Transporter and Facilitates Rhizosphere Competency in Metarhizium robertsii

2010

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The symbiotic associations between rhizospheric fungi and plants have enormous environmental impact. Fungi are crucial to plant health as antagonists of pathogens and herbivores and facilitate the uptake of soil nutrients. However, little is known about the plant products obtained by fungi in exchange or how they are transported through the symbiotic interface. Here, we demonstrate that sucrose and raffinose family oligosaccharides in root exudates are important for rhizosphere competence in the insect pathogen Metarhizium robertsii (formerly known as Metarhizium anisopliae). We identified mutants in the Metarhizium raffinose transporter (Mrt) gene of M. robertsii that grew poorly in root exudate and were greatly reduced in rhizosphere competence on grass roots. Studies on sugar uptake, including competition assays, revealed that MRT was a sucrose and galactoside transporter. Disrupting MRT resulted in greatly reduced or no growth on sucrose and galactosides but did not affect growth on monosaccharides or oligosaccharides composed entirely of glucose subunits. Consistent with this, expression of Mrt is exclusively up-regulated by galactosides and sucrose. Expressing a green fluorescent protein gene under the control of the Mrt promoter confirmed that MRT was expressed by germlings in the vicinity of grass roots but not in surrounding bulk soil. Disrupting Mrt did not reduce virulence to insects, demonstrating that Mrt is exclusively involved in M. robertsii's interactions with plants. To our knowledge, MRT is the first oligosaccharide transporter identified and characterized in a fungus and is unique to filamentous fungi, but homologous genes in Magnaporthe, Ustilago, Aspergillus, Fusarium, Epichloe, and Penicillium species indicate that oligosaccharide transport is of widespread significance.

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Cytosol-to-lysosome Transport of Free Polymannose-type Oligosaccharides

Cited by 62 publications

References 55 publications

Dual Functions for Cytosolic α-Mannosidase (Man2C1)

Dual Functions for Cytosolic α-Mannosidase (Man2C1)

Monoglucosylated Oligomannosides Are Released during the Degradation Process of Newly Synthesized Glycoproteins

Mrt, a Gene Unique to Fungi, Encodes an Oligosaccharide Transporter and Facilitates Rhizosphere Competency in Metarhizium robertsii

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