title: Reduction of interchain disulfide bonds precedes the dislocation of Ig-mu chains from the endoplasmic reticulum to the cytosol for proteasomal degradation.
abstract: Proteins that fail to fold or assemble in the endoplasmic reticulum (ER) are generally dislocated across the membrane to be degraded by cytosolic proteasomes. To investigate how the quality control machinery handles individual subunits that are part of covalent oligomers, we have analyzed the fate of transport-competent Ig light (L) chains that form disulfide bonds with short-lived mu heavy chains. When expressed alone, L chains are secreted. In cells producing excess mu, most L chains are retained in the ER as covalent mu-L or mu2-L2 complexes. While mu chains present in these complexes are degraded by proteasomes, L chains are stable. Few L chains are secreted; most reassociate with newly synthesized mu chains. Therefore, interchain disulfide bonds are reduced in the ER lumen before the dislocation of mu chains in a site from which freed L chains can be rapidly reinserted in the assembly line. The ER can thus sustain the simultaneous formation and reduction of disulfide bonds.
authors.affiliation: Department of Molecular Pathology and Medicine, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fagioli
authors.forename: A
authors.initials: A
authors.lastname: Mezghrani
authors.forename: R
authors.initials: R
authors.lastname: Sitia
mesh_terms: D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006868:Hydrolysis; D007148:Immunoglobulin mu-Chains / Q000737:chemistry / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004220:Disulfides; D007148:Immunoglobulin mu-Chains; D009097:Multienzyme Complexes; D011948:Receptors, Antigen, T-Cell; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex