earticle

영어

EDEM1 is an endoplasmic reticulum-associated protein degradation (ERAD) component. ERAD is a cellular pathway that targets misfolded and misassembled glycoproteins for degradation. EDEM1 is involved in the recognition of misfolded luminal glycoproteins and in routing them for dislocation to the cytosol, followed by their degradation. EDEM1 interacts with substrate glycoproteins after their exit from the calnexin/calreticulin cycle and after processing by ER-mannosidase I. Although EDEM1 was proposed to be lectin–like and to react with Man8GlcNAc2 oligosaccharides, itsmechanism of action and its fate are still largely unknown. In a previous report, we found that EDEM1 becomes rapidly degraded and that this occurs by basal autophagy. Here, we show that EDEM1 forms complexes with the selective autophagy receptor p62, NBR1 and Alfy. This was demonstrated in HepG2 cells by double immunogold electron microscopy. Furthermore, we show the interaction between p62 and EDEM1 by immunoprecipitation- Western blot experiments. By serial section analysis, the origin of the phagophore for selective autophagy of EDEM1 could be identified as modified parts of rough ER cisternae. Hence, we provide new insight into the details of EDEM1 degradation process.