Endosomal trafficking of the ligated FcɛRI receptor

In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcɛRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcɛRI. Here we demonstrate that in RBL-2H3 cells, aggregated FcɛRI appears in the early endosomal antigen 1 (EEA1+) domains of the early endosomes within 15 min after ligation. Minimal co-localization of FcɛRI with Rab5 was observed by 30 min, followed by its appearance in the Rab7+ late endosomes and lysosomes at later time points. During endosomal sorting, FcɛRIα and γ subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated FcɛRI within the endosomal–lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of FcɛRI in endosomes.