Liquid-liquid phase separation: Orchestrating cell signaling through time and space

Cell signaling is a complex process. The faithful transduction of information into specific cellular actions depends on the synergistic effects of many regulatory molecules, nurtured by their strict spatiotemporal regulation. Over the years, we have gained copious insights into the subcellular architecture supporting this spatiotemporal control, including the roles of membrane-bound organelles and various signaling nanodomains. Recently, liquid-liquid phase separation (LLPS) has been recognized as another potentially ubiquitous framework for organizing signaling molecules with high specificity and precise spatiotemporal control in cells. Here, we review the pervasive role of LLPS in signal transduction, highlighting several key pathways that intersect with LLPS, including examples in which LLPS is controlled by signaling events. We also examine how LLPS orchestrates signaling by compartmentalizing signaling molecules, amplifying signals non-linearly, and moderating signaling dynamics. We focus on the specific molecules that drive LLPS and highlight the known functional and pathological consequences of LLPS in each pathway.

Automated summary

Cell signaling is a complex process that relies on the synergistic effects of multiple regulatory molecules for the accurate transmission of information. Liquid-liquid phase separation (LLPS) has been identified as a potentially important framework for organizing signaling molecules in cells. LLPS plays a crucial role in signal transduction by compartmentalizing signaling molecules, amplifying signals, and moderating signaling dynamics.