Ribolla Lucrezia Maria, Patrone Marco, Degano Massimo, Ramella Martina, de Curtis Ivan
Vita-Salute San Raffaele University, Milan, Italy.
Cell Adhesion Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Commun Biol. 2025 Jul 11;8(1):1045. doi: 10.1038/s42003-025-08470-5.
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.
细胞迁移由支持运动性的分子网络精心编排。支架蛋白ERC1/ELKS和Liprin-α1通过组装动态的质膜相关平台来维持细胞迁移和侵袭。ERC1/ELKS形成具有类液体行为的细胞质凝聚物。在本研究中，我们测试了ERC1形成凝聚物的能力是否与其在细胞运动中的功能相关。我们确定了ERC1最短的N端区域，该区域足以在体外和细胞内驱动相分离。光漂白后的荧光恢复证实了ERC1(1-244)凝聚物的动态行为。令人惊讶的是，删除包括一个内在无序区域的ERC1(1-244)并没有消除ERC1DΔN形成凝聚物的能力。尽管ERC1ΔN与伙伴的相互作用未受影响，但ERC1ΔN凝聚物的生物物理特性发生了改变，对细胞运动产生了影响。这些发现突出了ERC1/ELKS组装功能网络的重要性，并表明改变ERC1驱动的凝聚物的特性会干扰肿瘤细胞的运动。
