Membrane nanoclusters of Fc gamma RI segregate from inhibitory SIRP alpha upon activation of human macrophages

作者：Lopes Filipa B; Balint Stefan; Valvo Salvatore; Felce James H; Hessel Edith M; Dustin Michael L; Davis Daniel M^*

来源：The Journal of Cell Biology, 2017, 216(4): 1123-1141.

DOI：10.1083/jcb.201608094

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.

• 出版日期2017-4