Abstract
Raft domains have been proposed to work as a platform where raftophilic signaling molecules assemble and interact for efficient signal transduction. However, this raft hypothesis has been difficult to prove. Our recent single-molecule tracking experiments revealed that cytoplasmic signaling molecules were frequently, but very transiently recruited to the rafts formed on demand by the clusters of raftophilic glycosylphosphatidylinositol (GPI)-anchored receptors (e.g., CD59) that were generated after the engagement of the receptors by the binding of extracellular signaling molecules. All of the cytoplasmic signaling molecules examined thus far, Gαi2, Lyn, and PLCγ, exhibited short residency times of ~200 ms within the CD59-cluster rafts. This recruitment period of each individual signaling molecule was short, compared with the periods of overall bulk activation of these molecules by a factor of 4,000. Argument has been advanced that the analogue bulk signal, which lasts for over several thousands seconds, is generated by the superposition of the short-lived, digital-like individual signals, which last for a fraction of a second.
