Résumé
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 µ heavy chains. When expressed alone, L chains are secreted. In cells producing excess µ, most L chains are retained in the ER as covalent µ·L or µ2·L2 complexes. While µ chains present in these complexes are degraded by proteasomes, L chains are stable. Few L chains are secreted; most reassociate with newly synthesized µ chains. Therefore, interchain disulfide bonds are reduced in the ER lumen before the dislocation of µ 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.