Biomolecular condensates in membrane receptor signaling

Clustering is a prominent feature of receptors at the plasma membrane (PM). It plays an important role in signaling. Liquid-liquid phase separation (LLPS) of proteins is emerging as a novel mechanism underlying the observed clustering. Receptors/transmembrane signaling proteins can be core components essential for LLPS (such as LAT or nephrin) or clients enriched at the phase-separated condensates (for example, at the postsynaptic density or at tight junctions). Condensate formation has been shown to regulate signaling in multiple ways, including by increasing protein binding avidity and by modulating the local biochemical environment. In moving forward, it is important to study protein LLPS at the PM of living cells, its interplay with other factors underlying receptor clustering, and its signaling and functional consequences.

Automated summary

Clustering of receptors at the plasma membrane is a prominent feature and is influenced by liquid-liquid phase separation of proteins. Proteins involved in LLPS can act as core components or be enriched at the condensates. Formation of condensates regulates signaling by increasing protein binding avidity and modulating the local biochemical environment. Further research is needed to explore the interplay between protein LLPS, receptor clustering, and their signaling and functional consequences at the plasma membrane of living cells.