Stoichiometry controls activity of phase-separated clusters of actin signaling proteins

Organized for action It is becoming increasingly clear that biomolecular condensates, which are concentrations of macromolecules not surrounded by a membrane, are a key organizational structure in eukaryotic cells (see the Perspective by Martin and Mittag). Now, two papers show how such condensates function in actin assembly or in a Ras signaling pathway. In both cases, the condensates form at the plasma membrane and increase the activity of signaling proteins by increasing their membrane dwell times. Caseet al. show that the dwell time is dependent on cluster stoichiometry, so that stoichiometry of regulatory proteins can control actin assembly. Huanget al. demonstrate that the longer dwell time allows kinetic proofreading in receptor-mediated activation of Ras.Science , this issue p.1093 , p.1098 ; see also p.1036