Receptor‐Free Signaling at Curved Cellular Membranes

Plasma membranes are subject to continuous deformations. Strikingly, some of these transient membrane undulations yield membrane‐associated signaling hubs that differ in composition and function, depending on membrane geometry and the availability of co‐factors. Here, recent advancements on this ubiquitous type of receptor‐independent signaling are reviewed, with a special focus on emerging concepts and technical challenges associated with studying these elusive signaling sites. Binding of ligands to transmembrane receptors induce signaling (left, blue). Similarly, membrane deformations trigger signaling hub formation (right, green). The composition of such transient signaling sites is determined via membrane geometry and the local lipid environment at the inner leaflet.