Large-scale molecular assemblies, or signaling clusters, at the cell membrane are emerging as important regulators of cell signaling. Here, we review new findings and describe shared characteristics common to signaling clusters from a diverse set of cellular systems. The well-known T cell receptor cluster serves as our paradigmatic model. Specifically, each cluster initiates recruitment of hundreds of molecules to the membrane, interacts with the actin cytoskeleton, and contains a significant fraction of the entire signaling process. Probed by recent advancements in patterning and microscopy techniques, the signaling clusters display functional outcomes that are not readily predictable from the individual components.
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