Abstract

Scaffolds are fundamental to many cellular signaling pathways. In this essay, a novel class of scaffolds are proposed, whose action bears striking resemblance to kinetic proofreading. Commonly, scaffold proteins are thought to work as tethers, bringing different components of a pathway together to improve the likelihood of their interaction. However, recent studies show that the cytoskeletal scaffold, anillin, supports contractile signaling by a novel, non‐tethering mechanism that controls the membrane dissociation kinetics of RhoA. More generally, such proof‐reading‐like scaffolds are distinguished from tethers by a rare type of cooperativity, manifest as a super‐linear relationship between scaffold concentration and signaling efficiency. The evidence for this hypothesis is reviewed, its conceptual ramifications are considered, and research questions for the future are discussed.