Disposal of Non-Glycosylated Polypeptides from the Mammalian ER
Research area: Controllo della produzione proteica
Group leaders: Maurizio Molinari
Status: In progress
To maintain ER homeostasis and to ensure the highest efficiency of functional polypeptide production, the quality control machinery operating in the mammalian ER must distinguish non-native intermediates of protein folding programs from terminally misfolded polypeptides. Folding intermediates must be retained in the ER to attain the native structure under the assistance of dedicated molecular chaperones and folding enzymes. Terminally misfolded polypeptides must be rapidly cleared from the ER lumen to avoid interferences with ongoing folding programs. For glycosylated polypeptides, which represent the majority of the cargo entering the secretory pathway, the processing of the N-linked oligosaccharides determines retention in the folding environment (cycles of removal/re-addition of terminal glucose residues) or extraction from the folding environment for disposal. Virtually nothing is known about quality control of non-glycosylated polypeptides. The aim of this project is the identification of ER-resident factors involved in quality control and disposal of both soluble and membrane-bound non-glycosylated variants of model glycopolypeptides generated in our lab.
Tannous et al., Semin Cell Dev Biol. 2015; in press