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

Journal article

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.

Authors: Lopes, F; Bálint, Š; Valvo, S; Felce, J; Hessel, E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Rockefeller University Press
• Journal: Journal of Cell Biology
• Volume: 216
• Issue: 4
• Pages: 1123-1141
• Publication date: 2017-03-13
• Acceptance date: 2017-01-30
• DOI: 10.1083/jcb.201608094
• EISSN: 1540-8140
• ISSN: 0021-9525
• Language: English
• Keywords: Journal Article