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. (shrink)

Although it is not their fault, Shors & Matzel's attempt to review the LTP and learning hypothesis suffers from there being no clear published statement of the idea. Their summary of relevant evidence is not without error, however, and it oversimplifies fundamental issues relating to NMDA receptor function. Their attentional hypothesis is intriguing but requires a better systems-level understanding of how attention contributes to cognitive function.