Altering the biophysical properties of ERC1/ELKS-driven condensates interferes with cell motility.

Cell migration is orchestrated by molecular networks supporting motility. The scaffolds ERC1/ELKS and Liprin-α1 sustain cell migration and invasion by assembling dynamic plasma membrane-associated platforms. ERC1/ELKS forms cytoplasmic condensates with liquid–like behavior. In this study we tested whether the ability of ERC1 to form condensates is relevant to its function in cell motility. We identified the shortest N-terminal region of ERC1 sufficient to drive phase separation in vitro and in cells. Fluorescence recovery after photobleaching confirmed the dynamic behavior of ERC1(1-244) condensates. Surprisingly, deletion of ERC1(1-244) including an intrinsically disordered region did not abolish the ability of ERC1DΔN to form condensates. Although the interactions of ERC1ΔN with partners were unaffected, the biophysical properties of ERC1ΔN condensates were altered, with consequences on cell motility. These findings highlight the importance of ERC1/ELKS to assemble functional networks, and show that altering the properties of ERC1–driven condensates interferes with tumor cell motility.