Protein Self-Assembly Senses Membrane Receptors

Uptake of membrane receptors via clathrin-mediated endocytosis is an essential part of cellular homeostasis and signal transduction. This process involves binding of receptors by adaptor proteins on the cytosolic side of the plasma membrane via specifically recognized cargo motifs. Adaptors then recruit clathrin to assemble a cage and begin the vesicle budding process. However, receptors are not strictly necessary for this recruitment and assembly, as seen in in vitro experiments. Here, we model how the presence of receptors influences the behavior of adaptors on the membrane, acting as a switch which can control the nucleation of clathrin coats. We develop analytical approximations for how receptor concentrations and adaptor affinities alter the membrane residence time of adaptor proteins that are highly accurate over a range of physiological conditions. We find that receptors stabilize adaptors on the membrane especially when the adaptors have weak affinity for the membrane, and, paradoxically, that the presence of multiple receptor types can be detrimental to adaptor residence time. Combined with a model of coat assembly, we show that coat nucleation can be tuned by adaptor residence time, allowing self-assembly to indirectly "sense" membrane receptors.