Glucosidase II beta Subunit Modulates N-Glycan Trimming in Fission Yeasts and Mammals

IVAN D. STIGLIANO,* JULIO J. CARAMELO,†‡ CARLOS A. LABRIOLA,* ARMANDO J. PARODI,* AND CECILIA D’ALESSIO*‡

molecular bilogy of the cell

American Society for Cell Biology

Lugar: United States; Año: 2009 vol. 20 p. 3974 - 3984

1939-4586

Glucosidase II (GII) plays a key role in glycoprotein biogenesis in the endoplasmic reticulum (ER). It is responsible forthe sequential removal of the two innermost glucose residues from the glycan (Glc3Man9GlcNAc2) transferred to Asnresidues in proteins. GII participates in the calnexin/calreticulin cycle; it removes the single glucose unit added to foldingintermediates and misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. GII is a heterodimer whosesubunit (GII) bears the glycosyl hydrolase active site, whereas its
subunit (GII
) role is controversial and has beenreported to be involved in GIIER retention and folding. Here, we report that in the absence of GII
, the catalytic subunitGII of the fission yeast Schizosaccharomyces pombe (an organism displaying a glycoprotein folding quality controlmechanism similar to that occurring in mammalian cells) folds to an active conformation able to hydrolyze p-nitrophenyl-D-glucopyranoside. However, the heterodimer is required to efficiently deglucosylate the physiological substratesGlc2Man9GlcNAc2 (G2M9) and Glc1Man9GlcNAc2 (G1M9). The interaction of the mannose 6-phosphate receptor homologousdomain present in GII
and mannoses in the B and/or C arms of the glycans mediates glycan hydrolysisenhancement. We present evidence that also in mammalian cells GII
modulates G2M9 and G1M9 trimming.