title: A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies.
abstract: Membrane proteins with transmembrane domains (TMDs) that contain polar residues exposed to the lipid bilayer are selectively sorted into multivesicular bodies (MVBs) and delivered to the yeast vacuole. Sorting of some, although not all, proteins into these structures is mediated by ubiquitination. We have identified a transmembrane ubiquitin ligase, Tul1, that is resident in the Golgi apparatus and is required for the ubiquitination of proteins with polar TMDs, including vacuolar proteins such as carboxypeptidase S. We suggest that Tul1 provides quality control, identifying misfolded membrane proteins and marking them for transport to endosomes and degradation in the vacuole.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.forename: Hugh R B
authors.initials: HR
authors.lastname: Pelham
mesh_terms: D000595:Amino Acid Sequence; D005456:Fluorescent Dyes / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D005964:Glucosyltransferases; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism; D008025:Ligases / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology*; D050765:Qa-SNARE Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D015003:Yeasts / Q000166:cytology / Q000235:genetics / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D005656:Fungal Proteins; D008565:Membrane Proteins; C081224:PEP12 protein, S cerevisiae; D021382:Protein Sorting Signals; D050765:Qa-SNARE Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C461959:TUL1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase; D008025:Ligases