title: Quality control of inner nuclear membrane proteins by the Asi complex.
abstract: Misfolded proteins in the endoplasmic reticulum (ER) are eliminated by a quality control system called ER-associated protein degradation (ERAD). However, it is unknown how misfolded proteins in the inner nuclear membrane (INM), a specialized ER subdomain, are degraded. We used a quantitative proteomics approach to reveal an ERAD branch required for INM protein quality control in yeast. This branch involved the integral membrane proteins Asi1, Asi2, and Asi3, which assembled into an Asi complex. Besides INM misfolded proteins, the Asi complex promoted the degradation of functional regulators of sterol biosynthesis. Asi-mediated ERAD was required for ER homeostasis, which suggests that spatial segregation of protein quality control systems contributes to ER function.
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), Carrer del doctor Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Carrer del doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Ombretta
authors.initials: O
authors.lastname: Foresti
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), Carrer del doctor Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Carrer del doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Rodriguez-Vaello
authors.affiliation: Electron Microscopy Core Facility, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Funaya
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), Carrer del doctor Aiguader 88, 08003 Barcelona, Spain. Universitat Pompeu Fabra, Carrer del doctor Aiguader 88, 08003 Barcelona, Spain. pedro.carvalho@crg.eu.
authors.forename: Pedro
authors.initials: P
authors.lastname: Carvalho
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D017353:Gene Deletion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C438144:ASI1 protein, S cerevisiae; C438145:ASI3 protein, S cerevisiae; C516922:Asi2 protein, S cerevisiae; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D003577:Cytochrome P-450 Enzyme System; C526348:Erg11 protein, S cerevisiae