期刊
JOURNAL OF CELL BIOLOGY
卷 216, 期 4, 页码 1123-1141出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201608094
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资金
- Medical Research Council [G1001044]
- Wellcome Trust [110091, 100262/Z/12/Z, 107375AIA]
- Manchester Collaborative Centre for Inflammation Research
- precompetitive open-innovation award from GlaxoSmith-Kline
- AstraZeneca
- University of Manchester, UK
- MRC [G1001044] Funding Source: UKRI
- Medical Research Council [G1001044] Funding Source: researchfish
- Wellcome Trust [110091/Z/15/Z] Funding Source: researchfish
- Wellcome Trust [110091/Z/15/Z] Funding Source: Wellcome Trust
Signal integration between activating Fc receptors and inhibitory signal regulatory protein alpha (SIRP alpha) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fc gamma receptor I (Fc gamma RI), Fc gamma RII, and SIRP alpha 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 Fc gamma RI, but not Fc gamma RII, are constitutively associated with nanoclusters of SIRPa, within 62 +/- 5 nm, mediated by the actin cytoskeleton. Upon Fc receptor activation, Src-family kinase signaling leads to segregation of Fc gamma RI and SIRPa nanoclusters to be 197 +/- 3 nm apart. Co-ligation of SIRPa with CD47 abrogates nanocluster segregation. If the balance of signals favors activation, Fc gamma RI 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.
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