Degradation of Misfolded Glycoproteins in the Endoplasmic Reticulum

  • Nobuko Hosokawa


Secretory proteins and membrane proteins are synthesized in the endoplasmic reticulum (ER), and only correctly folded or properly assembled proteins are sorted to the early secretory pathway, whereas proteins that failed to obtain correct conformations are retained in the ER, followed by intracellular protein degradation named ER-associated degradation (ERAD). This cellular function is called ER quality control (ERQC) (Ellgaard et al. 1999; Trombetta and Parodi 2003) (Fig. 1). Most of the proteins synthesized in the ER are N-glycosylated, by the attachment of high mannose oligosaccharides (Glc3Man9GlcNAc2) to the asparagine residues in the context of the consensus sequence of Asn-Xaa-Ser/Thr. The processing of the N-linked oligosaccharides plays an important role in the ERQC of glycoproteins. Removal and readdition of glucose at the terminus of the N-linked glycan contribute to the productive folding of glycoproteins in mammals, through the interaction with lectin chaperone calnexin and calreticulin. Trimming of the mannose residues, particularly from the middle branch of the N-linked glycan, is important for the entry into the ERAD pathway, but glycoproteins actually degraded seem to have Man8-5GlcNac2 glycans. We have cloned a mouse EDEM (ER-degradation enhancing α-mannosidase-like protein) (Hosokawa et al. 2001), and examined the function in glycoprotein ERAD.


Endoplasmic Reticulum Glycosylhydrolase Family Lectin Activity Normal Growth Medium Middle Branch 
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© Springer 2008

Authors and Affiliations

  • Nobuko Hosokawa
    • 1
  1. 1.Department of Molecular and Cellular Biology, Institute for Frontier Medical SciencesKyoto UniversityKyotoJapan

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