Endosomal trafficking of the ligated FcεRI receptor

In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (Fc epsilon RI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized Fc epsilon RI. Here we demonstrate that in RBL-2H3 cells, aggregated Fc epsilon RI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15 min after ligation, Minimal co-localization of Fc epsilon RI 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, Fc epsilon RI alpha and gamma 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 Fc epsilon RI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of Fc epsilon RI in endosomes. Published by Elsevier Ltd.