Misfolded GPI-anchored proteins are escorted through the secretory pathway by ER-derived factors

• DOI: 10.7554/elife.46740
• Publication Date: 2019-05-16T12:00:49Z
• Authors: Eszter Zavodszky; Ramanujan S Hegde
• Keywords: Endoplasmic-reticulum-associated protein degradation

We have used misfolded prion protein (PrP*) as a model to investigate how mammalian cells recognize and degrade GPI-anchored proteins. While most membrane proteins are degraded by proteasomes, primarily in lysosomes. Quantitative flow cytometry analysis showed that at least 85% of PrP* molecules transiently access the plasma en route Unexpectedly, time-resolved quantitative proteomics revealed remarkably invariant interactome during its trafficking from endoplasmic reticulum (ER) Hence, arrives complex with ER-derived chaperones cargo receptors. These interaction partners were critical for rapid endocytosis because induced misfold cell surface was not recognized effectively degradation. Thus, resident ER factors post-ER itineraries only shield their trafficking, but also provide quality control cue endocytic routing