title: Stimulation of ERAD of misfolded null Hong Kong alpha1-antitrypsin by Golgi alpha1,2-mannosidases.
abstract: Terminally misfolded or unassembled proteins are degraded by the cytoplasmic ubiquitin-proteasome pathway in a process known as ERAD (endoplasmic reticulum-associated protein degradation). Overexpression of ER alpha1,2-mannosidase I and EDEMs target misfolded glycoproteins for ERAD, most likely due to trimming of N-glycans. Here we demonstrate that overexpression of Golgi alpha1,2-mannosidase IA, IB, and IC also accelerates ERAD of terminally misfolded human alpha1-antitrypsin variant null (Hong Kong) (NHK), and mannose trimming from the N-glycans on NHK in 293 cells. Although transfected NHK is primarily localized in the ER, some NHK also co-localizes with Golgi markers, suggesting that mannose trimming by Golgi alpha1,2-mannosidases can also contribute to NHK degradation.
authors.affiliation: Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Saitama 332-0012, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hosokawa
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: You
authors.forename: Linda O
authors.initials: LO
authors.lastname: Tremblay
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
authors.forename: Annette
authors.initials: A
authors.lastname: Herscovics
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008358:Mannose / Q000737:chemistry; D008361:Mannosidases / Q000737:chemistry*; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D000515:alpha 1-Antitrypsin / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D000515:alpha 1-Antitrypsin; C065629:kifunensine; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase; D008358:Mannose