Steric masking of a dilysine endoplasmic reticulum retention motif during assembly of the human high affinity receptor for immunoglobulin E

Abstract

Signals that can cause retention in the ER have been found in the cytoplasmic domain of individual subunits of multimeric receptors destined to the cell surface. To study how ER retention motifs are masked during assembly of oligomeric receptors, we analyzed the assembly and intracellular transport of the human high-affinity receptor for immunoglobulin E expressed in COS cells. The cytoplasmic domain of the α chain contains a dilysine ER retention signal, which becomes nonfunctional after assembly with the γ chain, allowing transport out of the ER of the fully assembled receptor. Juxtaposition of the cytoplasmic domains of the α and γ subunits during assembly is responsible for this loss of ER retention. Substitution of the γ chain cytoplasmic domain with cytoplasmic domains of irrelevant proteins resulted in efficient transport out of the ER of the α chain, demonstrating that nonspecific steric hindrance by the cytoplasmic domain of the γ chain accounts for the masking of the ER retention signal present in the cytoplasmic domain of the α chain. Such a mechanism allows the ER retention machinery to discriminate between assembled and nonassembled receptors, and thus participates in quality control at the level of the ER.