The high-affinity immunoglobulin-E receptor (FcεRI) is endocytosed by an AP-2/clathrin-independent, dynamin-dependent mechanism

Gul'nar Fattakhova, Madhan Masilamani, Francisco Borrego, Alasdair M. Gilfillan, Dean D. Metcalfe, John E. Coligan

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Aggregation of the high-affinity immunoglobulin E (IgE) receptor (FcεRI), expressed on mast cells and basophils, initiates the immediate hypersensitivity reaction. Aggregated FcεRI has been reported to rapidly migrate to lipid rafts in RBL-2H3 cells. We confirmed that aggregated FcεRI is found in the lipid raft fractions of cellular lysates. Furthermore, we show that the cross-linked FcεRI remains associated with detergent-resistant structures upon internalization. Previous morphological studies have reported that aggregated FcεRI is endocytosed via clathrin-coated pits, which in general are not lipid raft associated. To address this apparent discrepancy, we employed siRNA to suppress expression of components of the clathrin-mediated internalization machinery, namely, clathrin heavy chain, and the AP-2 (α-adaptin or μ2-subunit). Transferrin receptor (TfR) is endocytosed by a clathrin-mediated process and, as expected, each transfected siRNA caused a two to threefold elevation of TfR surface expression and almost completely inhibited its endocytosis. In contrast, there was no effect on surface expression levels of FcεRI nor on the endocytosis of the dinitrophenyl-human serum albumin (DNP-HSA)/IgE/FcεRI complex. On the contrary, internalization of DNP-HSA/IgE/FcεRI was inhibited by overexpression of a dominant-negative dynamin mutant. We conclude that internalization of cross-linked FcεRI does not require the AP-2/ clathrin complex but is dynamin-dependent and may be lipid raft mediated.

Original languageEnglish
Pages (from-to)673-685
Number of pages13
JournalTraffic
Volume7
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Keywords

  • AP-2
  • Clathrin heavy chain
  • Dynamin
  • Endocytosis
  • FcεRI
  • siRNA

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