Receptor‐Free Signaling at Curved Cellular Membranes

Abstract

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.

A mechanosensing mechanism mediated by IRSp53 controls plasma membrane shape homeostasis at the nanoscale

“…The burst in actin polymerization at the evaginated PM and the simultaneous reattachment to the cortex suggest that the local topography generated by compression may act as the mechanical input triggering the subsequent polymerization event. Indeed, membrane curvature can recruit different signaling molecules (19,(34)(35)(36)(37), chief among them curvature-sensing BAR proteins (38)(39)(40)(41). The superfamily of BAR proteins includes molecules containing different curvature sensing and generating BAR domains: The N-BAR and F-BAR domains, which interact with positively curved membranes (invaginations), and the I-BAR domain for the opposite type of curvature (negatively curved membranes or evaginations).…”

Cholera Toxin as a Probe for Membrane Biology

“…This principle was first identified for the case of STxB and represents an example of a broader mechanism whereby lectins generate membrane curvature to drive endocytosis by binding to multiple glycolipids or glycoproteins (the GL-Lect hypothesis) [ 146 ]. Membrane curvature created by the extracellular CTxB could potentially lead to the recruitment of intracellular curvature-sensing proteins, in turn controlling the local membrane composition [ 147 , 148 ]. However, CTxB mutants capable of binding to only a single copy of GM1 can sort into preformed clathrin-independent endocytic structures, suggesting glycolipid clustering-induced curvature generation is dispensable for its uptake into at least a subset of CIE carriers [ 141 ].…”

Cellular Membranes, a Versatile Adaptive Composite Material

“…2.2 in Box 1 ). Adding hydrophobic heads with varying size further renders lipids curvature-sensitive, while differences in charge will influence protein-lipid interactions with peripheral cytosolic proteins ( Ebrahimkutty and Galic, 2019 ; Bassereau et al, 2018 ). The bending stiffness of the cell cortex, which is relevant in the μm regime, can be influenced by changes to the actin mesh size (depicted by the density of cortex linker proteins) or the thickness of the cortex itself.…”