Lectins of ERAD Pathway: F-Box Proteins and M-Type Lectins

Abstract

Glycoprotein folding and degradation in endoplasmic reticulum (ER) is mediated by ER quality control system. Quality control in ER ensures that only properly folded proteins are retained in the cell through mechanisms that recognize and discard misfolded or unassembled proteins in a process called endoplasmic reticulum-associated degradation (ERAD). The ERAD pathway comprises multiple steps including substrate recognition and targeting to the retro-translocation machinery, retrotranslocation from the ER into the cytosol, and proteasomal degradation through ubiquitination. Roles of lectin-type molecules for trimmed high-mannose type N-glycans and glycosidases in the ERAD pathways in both ER and cytosol has been documented in recent years. Yoshida et al. (2010) reviewed the fundamental system that monitors glycoprotein folding in the ER and the unique roles of sugar-recognizing ubiquitin ligase and peptide:N-glycanase (PNGase) in the cytosolic ERAD pathway. Mannose trimming plays an important role by forming specific N-glycans that permit the recognition and sorting of terminally misfolded conformers for ERAD. The EDEM (ER degradation enhancing α-mannosidase-like protein) subgroup of proteins belonging to Class I α1,2-mannosidase family (glycosylhydrolase family 47) has been shown to enhance ERAD. However, the mechanisms of substrate recognition and sorting to the ERAD pathway are poorly defined.