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Plasma membrane organization and the potential role, or not, of lipid raft microdomains in signal transduction is a controversial topic. Cross-correlation fluorescent correlation spectroscopy (CC-FCS) shows promise as a new approach to rapidly probe protein–protein interactions in living cells during signal transduction. CC-FCS data from studies of IgE receptor signaling challenge models of large stable lipid raft signaling domains and reveal a new complexity in the dynamic (re)organization of signaling complexes.

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