Compartmentalized IgE Receptor-mediated Signal Transduction in Living Cells

doi:10.1083/jcb.139.6.1447

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© The Rockefeller University Press, 0021-9525/1997//1447 $5.00
The Journal of Cell Biology, Volume 139, Number 6, , 1997 1447-1454

Article

Compartmentalized IgE Receptor–mediated Signal Transduction in Living Cells

Thomas P. Stauffer and Tobias Meyer

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710

Several receptor-mediated signal transduction pathways, includingEGF and IgE receptor pathways, have been proposed to be spatiallyrestricted to plasma membrane microdomains. However, the experimentalevidence for signaling events in these microdomains is largelybased on biochemical fractionation and immunocytochemical studiesand only little is known about their spatial dynamics in livingcells. Here we constructed green fluorescent protein–taggedSH2 domains to investigate where and when IgE receptor (Fc ${varepsilon}$ RI)–mediatedtyrosine phosphorylation occurs in living tumor mast cells.Strikingly, within minutes after antigen addition, tandem SH2domains from Syk or PLC- ${gamma}$ 1 translocated from a uniform cytosolicdistribution to punctuate plasma membrane microdomains. Colocalizationexperiments showed that the microdomains where tyrosine phosphorylationoccurred were indistinguishable from those stained by cholera toxin B, a marker for glycosphingolipids. Competitive bindingstudies with coelectroporated unlabeled Syk, PLC- ${gamma}$ 1, and otherSH2 domains selectively suppressed the induction of IgE receptor–mediatedcalcium signals as well as the binding of the fluorescent SH2domains. This supports the hypothesis that PLC- ${gamma}$ 1 and Syk SH2 domains selectively bind to Syk and IgE receptors, respectively.Unlike the predicted prelocalization of EGF receptors to caveolaemicrodomains, fluorescently labeled IgE receptors were foundto be uniformly distributed in the plasma membrane of unstimulatedcells and only transiently translocated to glycosphingolipidrich microdomains after antigen addition. Thus, these in vivostudies support a plasma membrane signaling mechanism by whichIgE receptors transiently associate with microdomains and inducethe spatially restricted activation of Syk and PLC- ${gamma}$ 1.

Abbreviations used in this paper: GFP, green fluorescent protein; GST, glutathione-S-transferase; ITAM, immunoreceptor tyrosine-based activation motifs; PI, phosphatydilinositol; PLC, phospholipase C.

T.P. Stauffer is a recipient of a fellowship from the SwissNational Science Foundation (Grant 823A-050457). T. Meyer wassupported by a fellowship from the David and Lucile PackardFoundation. This work was supported by Proctor & Gamblegrant SRA 1617 and the National Institutes of Health grantsGM-48113 and GM-51457.

Address all correspondence to Tobias Meyer, Department of CellBiology, Nanaline Duke Building, Room #346, Box 3709, DUMC,Durham, NC 27710. Tel.: (919) 681-8072. Fax: (919) 681-7978.E-mail: tobias{at}cellbio.duke.edu

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