title: Basal autophagy is involved in the degradation of the ERAD component EDEM1.
abstract: Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol and is degraded by basal autophagy.
authors.affiliation: Department of Pathology, University of Zurich, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Le Fourn
authors.forename: K
authors.initials: K
authors.lastname: Gaplovska-Kysela
authors.forename: B
authors.initials: B
authors.lastname: Guhl
authors.forename: R
authors.initials: R
authors.lastname: Santimaria
authors.forename: C
authors.initials: C
authors.lastname: Zuber
authors.forename: J
authors.initials: J
authors.lastname: Roth
mesh_terms: D001343:Autophagy; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport
chemical_list: C486654:EDEM1 protein, human; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex