Transport of the IgE Receptor α-Chain Is Controlled by a Multicomponent Intracellular Retention Signal

The human high affinity IgE receptor (FcϵRI) is a central component of the allergic response and is expressed as either a trimeric αγ2 or tetrameric αβγ2 complex. It has been previously described that the cytoplasmic domain (CD) of the α-chain carries a dilysine motif at positions -3/-7 from the C t...

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Veröffentlicht in:The Journal of biological chemistry 2006-04, Vol.281 (15), p.10448-10460
Hauptverfasser: Cauvi, David M., Tian, Xufang, von Loehneysen, Katharina, Robertson, Michael W.
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Sprache:eng
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Zusammenfassung:The human high affinity IgE receptor (FcϵRI) is a central component of the allergic response and is expressed as either a trimeric αγ2 or tetrameric αβγ2 complex. It has been previously described that the cytoplasmic domain (CD) of the α-chain carries a dilysine motif at positions -3/-7 from the C terminus that functions in intracellular retention prior to assembly with other FcϵRI subunits. In this report we have further explored the role of the -3/-7 dilysine signal in controlling steady-state α-chain transport by mutational analysis and found little surface expression of a -3/-7 dialanine α-chain mutant but significant Golgi localization. We compared the transport properties of a series of α-chain cytoplasmic domain truncation mutants and observed that truncation mutants lacking 23 or more C-terminal residues showed a dramatic increase in steady-state transport suggesting a role for the membrane-proximal CD sequence in α-chain retention. By performing alanine-scanning mutagenesis we identified a dilysine sequence (Lys212-Lys216) proximal to the transmembrane domain (TMD) that is important for both α-chain cell-surface expression and intracellular stability. Furthermore, co-mutation of the Lys212-Lys216 residues with the -3/-7 dilysine signal produced a dramatic increase in α-chain surface expression that was further increased by co-mutation of the lone charged residue (Asp192) in the TMD thereby defining three regions that function to regulate α-chain transport and in a highly synergistic manner.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M510751200