title: The chaperone BAG6 captures dislocated glycoproteins in the cytosol.
abstract: Secretory and membrane (glyco)proteins are subject to quality control in the endoplasmic reticulum (ER) to ensure that only functional proteins reach their destination. Proteins deemed terminally misfolded and hence functionally defective may be dislocated to the cytosol, where the proteasome degrades them. What we know about this process stems mostly from overexpression of tagged misfolded proteins, or from situations where viruses have hijacked the quality control machinery to their advantage. We know of only very few endogenous substrates of ER quality control, most of which are degraded as part of a signaling pathway, such as Insig-1, but such examples do not necessarily represent terminally misfolded proteins. Here we show that endogenous dislocation clients are captured specifically in association with the cytosolic chaperone BAG6, or retrieved en masse via their glycan handle.
authors.affiliation: Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Jasper H L
authors.initials: JH
authors.lastname: Claessen
authors.affiliation: Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Sumana
authors.initials: S
authors.lastname: Sanyal
authors.affiliation: Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D015153:Blotting, Western; D003600:Cytosol / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones / Q000378:metabolism*
chemical_list: C092009:BAG6 protein, human; D006023:Glycoproteins; D018832:Molecular Chaperones