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

STIGLIANO I, CARAMELO J. LABRIOLA C, PARODI A, DALESSIO C

MOLECULAR BIOLOGY OF THE CELL

AMER SOC CELL BIOLOGY

Año: 2009 vol. 20 p. 3974 - 3984

1059-1524

Glucosidase II (GII) plays a key role in glycoprotein biogenesis in the endoplasmic reticulum (ER). It is responsible for the sequential removal of the two innermost glucose residues from the glycan (Glc3Man9GlcNAc2) transferred to Asn residues in proteins. GII participates in the calnexin/calreticulin cycle; it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. GII is a heterodimer whose a subunit (GIIa) bears the glycosyl hydrolase active site, whereas its B subunit (GIIB) role is controversial and has been reported to be involved in GIIB ER retention and folding. Here, we report that in the absence of GIIB, the catalytic subunit GIIB of the fission yeast Schizosaccharomyces pombe (an organism displaying a glycoprotein folding quality control mechanism similar to that occurring in mammalian cells) folds to an active conformation able to hydrolyze p-nitrophenyl a-D-glucopyranoside. However, the heterodimer is required to efficiently deglucosylate the physiological substrates Glc2Man9GlcNAc2 (G2M9) and Glc1Man9GlcNAc2 (G1M9). The interaction of the mannose 6-phosphate receptor homologous domain present in GIIB and mannoses in the B and/or C arms of the glycans mediates glycan hydrolysis enhancement. We present evidence that also in mammalian cells GIIB modulates G2M9 and G1M9 trimming.