Letting go of O-glycans

Haddas Saad,Chaitanya Patel,Gerardo Z Lederkremer

doi:10.1074/jbc.h119.011245

Abstract

The generation of free N-glycans, or unconjugated oligosaccharides derived from N-linked glycoproteins, is well understood, but whether a similar fate awaits O-linked glycoprotein carbohydrates was unknown. Hirayama et al. now reveal, by using only mannose as an energy source, the generation of free O-glycans in Saccharomyces cerevisiae, in the lumen of a secretory compartment, possibly the vacuole. These findings uncover the presence of a possible regulated degradation pathway for O-mannosylated glycoproteins.

Highlights

The generation of free N-glycans, or unconjugated oligosaccharides derived from N-linked glycoproteins, is well understood, but whether a similar fate awaits O-linked glycoprotein carbohydrates was unknown
N-Linked glycosylation is performed in the ER,2 where it is tied to quality control events in protein folding; progressive trimming of the N-glycans before their removal serves as a code for glycoprotein folding status
The misfolded glycoproteins are retrotranslocated from the ER to the cytosol, where, before proteasomal degradation, they are exposed to PNGase, a glycosidase that releases the N-glycans from asparagine residues, producing free N-glycans (FNGs) (Fig. 1)

Summary

Introduction

The generation of free N-glycans, or unconjugated oligosaccharides derived from N-linked glycoproteins, is well understood, but whether a similar fate awaits O-linked glycoprotein carbohydrates was unknown. O- and N-glycosylation are involved in various biological processes, including immune responses; protein quality control, targeting, and degradation; signal transduction; cell interactions and differentiation; and other crucial processes [1]. The misfolded glycoproteins are retrotranslocated from the ER to the cytosol, where, before proteasomal degradation, they are exposed to PNGase, a glycosidase that releases the N-glycans from asparagine residues, producing free N-glycans (FNGs) (Fig. 1).

Results

Conclusion