STERIC MASKING OF A DILYSINE ENDOPLASMIC-RETICULUM RETENTION MOTIF DURING ASSEMBLY OF THE HUMAN HIGH-AFFINITY RECEPTOR FOR IMMUNOGLOBULIN-E

Signals that can cause retention in the ER have been found in the cyto plasmic domain of individual subunits of multimeric receptors destined to the cell surface. To study how ER retention motifs are masked duri ng assembly of oligomeric receptors, we analyzed the assembly and intr acellular transport of the human high-affinity receptor for immunoglob ulin E expressed in COS cells. The cytoplasmic domain of the alpha cha in contains a dilysine ER retention signal, which becomes nonfunctiona l after assembly with the gamma chain, allowing transport out of the E R of the fully assembled receptor. Juxtaposition of the cytoplasmic do mains of the alpha and gamma subunits during assembly is responsible f or this loss of ER retention. Substitution of the gamma chain cytoplas mic domain with cytoplasmic domains of irrelevant proteins resulted in efficient transport out of the ER of the alpha chain, demonstrating t hat nonspecific steric hindrance by the cytoplasmic domain of the gamm a chain accounts for the masking of the ER retention signal present in the cytoplasmic domain of the alpha chain. Such a mechanism allows th e ER retention machinery to discriminate between assembled and nonasse mbled receptors, and thus participates in quality control at the level of the ER.