Export of the high affinity IgE receptor from the endoplasmic reticulum depends on a glycosylation-mediated quality control mechanism

B Albrecht, M Woisetschläger… - The Journal of …, 2000 - journals.aai.org
B Albrecht, M Woisetschläger, MW Robertson
The Journal of Immunology, 2000journals.aai.org
The high affinity IgE receptor (FcεRI) is a multisubunit complex comprised of either αγ 2 or
αβγ 2 chains. The cotranslational assembly of the IgE-binding α-chain with a dimer of γ-
chains occurs in a highly controlled manner and is proposed to involve masking of a dilysine
motif present at the cytoplasmic C terminus of the FcεRI α-chain that targets localization of
this subunit to the endoplasmic reticulum (ER). Here, we show that ER quality control
modulates export from the ER of newly synthesized αγ 2 and αβγ 2 receptors. We …
Abstract
The high affinity IgE receptor (FcεRI) is a multisubunit complex comprised of either αγ 2 or αβγ 2 chains. The cotranslational assembly of the IgE-binding α-chain with a dimer of γ-chains occurs in a highly controlled manner and is proposed to involve masking of a dilysine motif present at the cytoplasmic C terminus of the FcεRI α-chain that targets localization of this subunit to the endoplasmic reticulum (ER). Here, we show that ER quality control modulates export from the ER of newly synthesized αγ 2 and αβγ 2 receptors. We demonstrate that the presence of untrimmed N-linked core glycans (Glc 3 Man 9 GlcNAc 2) on the FcεRI α-chain activates the ER quality control mechanism to retain this subunit in the ER, despite the presence of γ-chains. At the same time, the untrimmed, ER-localized α-chain exhibits IgE-binding activity, suggesting that FcεRI α-chain folding occurs before constitutive glucose trimming. In additional experiments, we demonstrate that cell surface expression of an α-chain C-terminal truncation mutant is also dependent on glucose trimming, but not on γ-chain coexpression. We suggest that glucosidase trimming of terminal glucose residues is a critical control step in the export of FcεRIα from the ER. Finally, we show that the constitutive ER FcεRI α-chain, expressed in the absence of the other FcεRI subunits, associates with the ER lectin-like chaperone calnexin, but not the structurally similar ER chaperone calreticulin, presumably through interaction with monoglucosylated α-chain ER glycoforms.
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