Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages
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 distribut...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Rockefeller University Press
2017
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| _version_ | 1797071949337198592 |
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| author | Lopes, F Bálint, Š Valvo, S Felce, J Hessel, E Dustin, M Davis, D |
| author_facet | Lopes, F Bálint, Š Valvo, S Felce, J Hessel, E Dustin, M Davis, D |
| author_sort | Lopes, F |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:00:31Z |
| format | Journal article |
| id | oxford-uuid:61f05442-bbc4-4e12-a12c-fb8d919f0eb6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:00:31Z |
| publishDate | 2017 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:61f05442-bbc4-4e12-a12c-fb8d919f0eb62022-03-26T18:03:09ZMembrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophagesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:61f05442-bbc4-4e12-a12c-fb8d919f0eb6EnglishSymplectic Elements at OxfordRockefeller University Press2017Lopes, FBálint, ŠValvo, SFelce, JHessel, EDustin, MDavis, DSignal 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. |
| spellingShingle | Lopes, F Bálint, Š Valvo, S Felce, J Hessel, E Dustin, M Davis, D Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages |
| title | Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages |
| title_full | Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages |
| title_fullStr | Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages |
| title_full_unstemmed | Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages |
| title_short | Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages |
| title_sort | membrane nanoclusters of fcγri segregate from inhibitory sirpα upon activation of human macrophages |
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