Structural aspects of the association of Fc epsilon RI with detergent-resistant membranes

We recently showed that aggregation of the high affinity IgE receptor on ma st cells, Fc epsilon RI, causes this immunoreceptor to associate rapidly wi th specialized regions of the plasma membrane, where it is phosphorylated b y the tyrosine kinase Lyn, In this study, we further characterize the deter gent sensitivity of this association on rat basophilic leukemia-2H3 mast ce lls, and we compare the capacity of structural variants of Fc epsilon RI an d other receptors to undergo this association. We show that this interactio n is not mediated by the beta subunit of the receptor or the cytoplasmic ta il of the gamma subunit, both of which are involved in signaling. Using chi meric receptor constructs, we found that the ex tracellular segment of the Fc epsilon RI alpha subunit was not sufficient to mediate this association, implicating Fc epsilon RI alpha and/or gamma transmembrane segments. To de termine the specificity of this interaction, we compared the association of several other receptors, Interleukin-1 type I receptors on Chinese hamster ovary cells and alpha 4-integrins on rat basophilic leukemia cells showed little or no association with isolated membrane domains, both before and af ter aggregation on the cells. In contrast, interleukin-2 receptor or (Tac) on Chinese hamster ovary cells exhibited aggregation-dependent membrane dom ain association similar to Fc epsilon RI, These results provide insights in to the structural basis and selectivity of lipid-mediated interactions betw een certain transmembrane receptors and detergent-resistant membranes.