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Vol. 18, Issue 4, 1410-1420, April 2007

This Article Full Text Full Text (PDF) Supplemental Materials A correction has been published All Versions of this Article: E05-11-1073v1 18/4/1410    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xue, M. Articles by Wilson, B. S. Search for Related Content PubMed PubMed Citation Articles by Xue, M. Articles by Wilson, B. S.

Activated N-Formyl Peptide Receptor and High-Affinity IgE Receptor Occupy Common Domains for Signaling and Internalization

Mei Xue^*,, Genie Hsieh, Mary Ann Raymond-Stintz^*, Janet Pfeiffer^*, Diana Roberts, Stanly L. Steinberg, Janet M. Oliver^*, Eric R. Prossnitz, Diane S. Lidke^*, and Bridget S. Wilson^*

*Department of Pathology and Cancer Research and Treatment Center, and Departments of Cell Biology and Physiology, Mathematics and Statistics, and Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM 87131

Submitted November 23, 2005; Revised January 8, 2007; Accepted January 24, 2007
Monitoring Editor: Jennifer Lippincott-Schwartz

Immune cells display multiple cell surface receptors that integrate signals for survival, proliferation, migration, and degranulation. Here, immunogold labeling is used to map the plasma membrane distributions of two separate receptors, the N-formyl peptide receptor (FPR) and the high-affinity IgE receptor (FRI). We show that the FPR forms signaling clusters in response to monovalent ligand. These domains recruit G_i, followed by the negative regulatory molecule arrestin2. There are low levels of colocalization of FPR with FcRI in unstimulated cells, shown by computer simulation to be a consequence of receptor density. Remarkably, there is a large increase in receptor coclustering when cells are simultaneously treated with N-formyl-methionyl-leucyl-phenylalanine and IgE plus polyvalent antigen. The proximity of two active receptors may promote localized cross-talk, leading to enhanced inositol-(3,4,5)-trisphosphate production and secretion. Some cointernalization and trafficking of the two receptors can be detected by live cell imaging, but the bulk of FPR and FcRI segregates over time. This segregation is associated with more efficient internalization of cross-linked FcRI than of arrestin-desensitized FPR. The observation of receptors in lightly coated membrane invaginations suggests that, despite the lack of caveolin, hematopoietic cells harbor caveolae-like structures that are candidates for nonclathrin-mediated endocytosis.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Bridget Wilson (bwilson{at}salud.unm.edu)

Abbreviations used: BCR, B cell receptor; DNP-BSA, dinitrophenol-conjugated bovine serum albumin; GFP, green fluorescent protein; FcRI, high-affinity receptor for IgE; fMLF, N-formyl-methionyl-leucyl-phenylalanine; FPR, N-formyl peptide receptor; TCR, T-cell receptor.