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Cotranslational endoplasmic reticulum assembly of FcɛRI controls the formation of functional IgE-binding receptors

By Edda Fiebiger, Domenico Tortorella, Marie-Helene Jouvin, Jean-Pierre Kinet and Hidde L. Ploegh

Abstract

The human high affinity receptor for IgE (FcɛRI) is a cell surface structure critical for the pathology of allergic reactions. Human FcɛRI is expressed as a tetramer (αβγ2) on basophils or mast cells and as trimeric (αγ2) complex on antigen-presenting cells. Expression of the human α subunit can be down-regulated by a splice variant of FcɛRIβ (βvar). We demonstrate that FcɛRIα is the core subunit with which the other subunits assemble strictly cotranslationally. In addition to αβγ2 and αγ2, we demonstrate the presence of αβ and αβvarγ2 complexes that are stable in the detergent Brij 96. The role of individual FcɛRI subunits for the formation of functional, immunoglobulin E–binding FcɛRI complexes during endoplasmic reticulum (ER) assembly can be defined as follows: β and γ support ER insertion, signal peptide cleavage and proper N-glycosylation of α, whereas βvar allows accumulation of α protein backbone. We show that assembly of FcɛRI in the ER is a key step for the regulation of surface expression of FcɛRI. The ER quality control system thus regulates the quantity of functional FcɛRI, which in turn controls onset and persistence of allergic reactions

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2212795
Provided by: PubMed Central
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