iTRVZ: liquid nano-platform for signal integration on the plasma membrane

Crosstalk of cellular signaling pathways is essential for coordinated cell responses. Therefore, we suspect the existence of scaffolding platforms that specifically undertake signal crosstalk and integration. Using advanced single-molecule imaging, we found a nanometer-scale liquid-like platform for integrating the signals downstream from GPI-anchored receptors and receptor-type tyrosine kinases. The platform employs some of the focal adhesion proteins, including integrin, talin, RIAM, VASP, and zyxin, but is distinct from focal adhesions, and is thus termed iTRVZ. The iTRVZ formation is driven by the protein liquid-liquid phase separation and the interactions with the raft domains in the plasma membrane and cortical actin. iTRVZ non-linearly integrates the two distinctly different receptor signals, and thus works as an AND gate and noise filter. One-Sentence Summary Nanometer-scale liquid-like protein platform for signal integration working as an AND gate was found on the plasma membrane. ### Competing Interest Statement The authors have declared no competing interest.