Glucosidase II and<i>N</i>-glycan mannose content regulate the half-lives of monoglucosylated species in vivo

Stigliano, Ivan Daniel; Alculumbre, Solana; Labriola, Carlos; Parodi, Armando J.; D’Alessio, Cecilia

doi:10.1091/mbc.e11-01-0019

Cited by 43 publications

(55 citation statements)

References 47 publications

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“…We have shown previously that a decrease in N-glycan mannose content sharply decreases in vivo GII activity without affecting the activity of UGGT, thereby prolonging the half-life of monoglucosylated glycans produced by UGGT (15). We speculate that ER mannosidase-mediated removal of mannose units would result in an increased interaction of slow folding/misfolded glycoproteins with the lectin chaperones.…”

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confidence: 82%

“…Spectral data were processed using NMRPipe (28) and visualized using XEASY (29). Complete 1 H, 15 N, and 13 C resonance assignments for GII␤ MRH domain were obtained in a semiautomated manner using peak lists from three-dimensional HNCO, HNCOCA, HNCOCACB, HNCA, HNCACB, HNCACO, CCONH, HBHACONH, HCCONH, and HCCH total correlation spectroscopy and 13 C (aromatic)-edited NOESY-HSQC spectra and the assignment program GARANT (30). Automated assignments were verified and completed by manual inspection.…”

Section: S Pombe Microsomal Fraction Preparations-s Pombementioning

confidence: 99%

“…Structures of the GII␤ MRH domain were calculated using distance constraints derived from three-dimensional 15 N-edited NOESY-HSQC and 13 C-edited NOESY-HSQC spectra ( mix ϭ 80 ms). Backbone and dihedral angle constraints were generated using TALOSϩ (31) and the secondary shifts of the 1 H, 13 C␣, 13 C␤, 13 CЈ, and 15 N nuclei. Initial structures were generated in an automated manner using the NOEASSIGN module of the torsion angle dynamics program CYANA (32).…”

Section: S Pombe Microsomal Fraction Preparations-s Pombementioning

confidence: 99%

“…Determination of Binding Affinities by Heteronuclear NMR Spectroscopy-NMR studies in which 15 N-labeled GII␤ MRH domain was titrated with increasing concentrations of ligand (Man-6-P (Sigma), Man␣1,2Man (Dextra Laboratories), or Man 9 GlcNAc purified from soybean agglutinin were carried out as described previously (35).…”

Section: S Pombe Microsomal Fraction Preparations-s Pombementioning

confidence: 99%

“…Furthermore, in vivo and cell free assays show that a decrease in N-glycan mannose content results in lower GII enzymatic activity (11)(12)(13)(14)(15). Not only does optimal GII deglucosylation activity require the presence of the full complement of mannose units on nascent glycoproteins but also the four conserved amino acids of the GII␤ subunit that are known to be essential for the ability of the MRH domains of MPRs to bind mannose 6-phosphate (Man-6-P)-containing lysosomal enzymes (15,16) (Fig. 2B).…”

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confidence: 99%

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Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

Olson

Orsi

Alculumbre

et al. 2013

Journal of Biological Chemistry

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Background: Glucosidase II is an endoplasmic reticulum enzyme involved in quality control of glycoprotein folding. Results: The structure of the lectin domain of GII was determined by NMR spectroscopy. Conclusion: GII lectin domain structure contains a unique Trp residue critical for GII activity. Significance: GII␤ MRH domain structure is the first determined of an MRH domain present in a protein with enzymatic activity.

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mentioning

confidence: 82%

Section: S Pombe Microsomal Fraction Preparations-s Pombementioning

confidence: 99%

Section: S Pombe Microsomal Fraction Preparations-s Pombementioning

confidence: 99%

Section: S Pombe Microsomal Fraction Preparations-s Pombementioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

Olson

Orsi

Alculumbre

et al. 2013

Journal of Biological Chemistry

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Expression of α‐subunit of α‐glucosidase II in adult mouse brain regions and selected organs

Anji

Miller

Chandrasekar

et al. 2014

J of Neuroscience Research

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Alpha glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in folding of nascent glycoproteins, is heterodimeric consisting of alpha (GIIα) and beta (GIIβ) subunits. The catalytic GIIα subunit with the help of mannose 6-phosphate receptor homology (MRH) domain of GIIβ sequentially hydrolyzes two α-1-3-linked glucose residues in the 2nd step of N-linked oligosaccharide-mediated protein folding. The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. N-glycosylation and correct protein folding is crucial for protein stability, trafficking, and cell surface expression of several proteins in the brain. Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies such as viral infection, cancer and diabetes. In spite of the widespread usage of GIIα inhibitory drugs and the role of GIIα in brain function little is known about its expression in brain and other tissues. Here, we report generation of a highly specific chicken antibody to GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. Using this antibody we show that the GIIα protein is highly expressed in testis, kidney, and lung, with the least amount in heart. GIIα polypeptide levels in whole brain were comparable to spleen. However, higher expression of GIIα protein was detected in cerebral cortex reflecting its continuous requirement in correct folding of cell surface proteins.

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Interaction mode between catalytic and regulatory subunits in glucosidase II involved in ER glycoprotein quality control

et al. 2016

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The glycoside hydrolase family 31 (GH31) α-glucosidases play vital roles in catabolic and regulated degradation, including the α-subunit of glucosidase II (GIIα), which catalyzes trimming of the terminal glucose residues of N-glycan in glycoprotein processing coupled with quality control in the endoplasmic reticulum (ER). Among the known GH31 enzymes, only GIIα functions with its binding partner, regulatory β-subunit (GIIβ), which harbors a lectin domain for substrate recognition. Although the structural data have been reported for GIIα and the GIIβ lectin domain, the interaction mode between GIIα and GIIβ remains unknown. Here, we determined the structure of a complex formed between GIIα and the GIIα-binding domain of GIIβ, thereby providing a structural basis underlying the functional extension of this unique GH31 enzyme.

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Glucosidase II andN-glycan mannose content regulate the half-lives of monoglucosylated species in vivo

Cited by 43 publications

References 47 publications

Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

Expression of α‐subunit of α‐glucosidase II in adult mouse brain regions and selected organs

Interaction mode between catalytic and regulatory subunits in glucosidase II involved in ER glycoprotein quality control

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