Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages

Filipa Lopes, Stefan Balint, Salvatore Valvo, James H. Felce, Edith M. Hessel, Michael L Dustin, Daniel Davis

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Abstract

Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton. Upon Fc receptor activation, Src-family kinase signaling leads to segregation of FcγRI and SIRPα nanoclusters to be 197 ± 3 nm apart. Co-ligation of SIRPα with CD47 abrogates nanocluster segregation. If the balance of signals favors activation, FcγRI nanoclusters reorganize into periodically spaced concentric rings. Thus, a nanometer- and micron-scale reorganization of activating and inhibitory receptors occurs at the surface of human macrophages concurrent with signal integration.
Original languageEnglish
Pages (from-to)1123–1141
JournalThe Journal of cell biology
Volume216
Issue number4
DOIs
Publication statusPublished - 13 Mar 2017

Keywords

  • macrophages
  • immune synapse
  • immunology

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