Fc receptor γ chain residues at the interface of the cytoplasmic and transmembrane domains affect association with FcαRI, surface expression, and function

Bruce D. Wines, Halina M. Trist, Renato C. Monteiro, Cees Van Kooten, P. Mark Hogarth

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

The assembly of multiple subunit immunoreceptors is dependent on transmembrane interactions. The Fc receptor γ (FcR-γ) chain is a ubiquitous immune receptor tyrosine-based activation motif-containing dimeric subunit, γ2, which in humans associates with both the activating members of the leukocyte receptor cluster, including the IgA receptor FcαRI, and the classical Fc receptors, including the IgE receptor FcαRI. This study identifies a new site in the transmembrane region of FcR-γ that affects receptor assembly and surface expression with FcαRI but not with FcαRI. The wild type complex, FcαRI-γ2 WT, remains robustly associated in both Brij-96 and Thesit detergent conditions. However, mutation of either Tyr25 or Cys26 of FcR-γ, near the interface of the transmembrane and cytoplasmic regions, resulted in impaired FcR-γ association with FcαRI. This association was disrupted in the presence of the detergent Brij-96 but was preserved in milder conditions using the detergent Thesit. Ligand-mediated cross-linking of the FcαRI-γ2Y25F mutant receptor resulted in diminished signal transduction, including an abnormal calcium response, compared with the FcαRI-γ2WT receptor. Furthermore, the FcαRI-γ2Y25F mutant receptor was expressed at the cell surface at ∼10% of that of the wild type, whereas the surface expression of FcεRI-γ2Y25F was not significantly different from the wild type. In contrast, although the FcαRI- γ2C26S mutant was also less stably associated, it was not reduced in surface expression or function. Thus, these TM residues of FcR-γ are important for association with FcαRI and probably other activating LRC members but not with the classical FcR, FcεRI.

Original languageEnglish
Pages (from-to)26339-26345
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number25
DOIs
Publication statusPublished - 18 Jun 2004
Externally publishedYes

Cite this