title: Sec61p is required for ERAD-L: genetic dissection of the translocation and ERAD-L functions of Sec61P using novel derivatives of CPY.
abstract: Misfolded proteins in the endoplasmic reticulum (ER) are exported to the cytosol for degradation by the proteasome in a process known as ER-associated degradation (ERAD). CPY* is a well characterized ERAD substrate whose degradation is dependent upon the Hrd1 complex. However, although the functions of some of the components of this complex are known, the nature of the protein dislocation channel remains obscure. Sec61p has been suggested as an obvious candidate because of its role as a protein-conducting channel through which polypeptides are initially translocated into the ER. However, it has not yet been possible to functionally dissect any role for Sec61p in dislocation from its essential function in translocation. By changing the translocation properties of a series of novel ERAD substrates, we are able to separate these two events and find that functional Sec61p is essential for the ERAD-L pathway.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Willer
authors.forename: Gabriella M A
authors.initials: GM
authors.lastname: Forte
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Stirling
mesh_terms: D002268:Carboxypeptidases / Q000737:chemistry / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005838:Genotype; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D008957:Models, Genetic; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014178:Translocation, Genetic
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009841:Oligonucleotides; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002268:Carboxypeptidases; C520242:CPY protein, S cerevisiae