FBS Colloquia No.387Laboratory of Single Molecule Biology

Ras activators RasGEFX/B/U/M driving spontaneous amoeboid cell migration

Cell migration is a fundamental cellular function that underlies various physiological processes such as nutrient exploration, immune responses, and morphogenesis. Ras family small GTPases are key molecules that generate signals for driving cell migration. The active form of Ras, Ras-GTP, can generate an asymmetric Ras-GTP-enriched signaling domain on the plasma membrane establishing front-rear polarity in motile cells. At Ras-GTP-enriched regions, actin polymerization is promoted leading to pseudopod formation. However, the molecular mechanisms controlling the spontaneous formation of asymmetric Ras signaling remain unknown. In this study, we focused on Ras guanine nucleotide exchange factors (RasGEFs) to identify those that regulate spontaneous Ras activation and to investigate their regulation mechanisms and how they contribute to the driving of cell migration. We identified RasGEFX as a Ras activator that drives spontaneous cell migration. Furthermore, our findings suggest that RasGEFX cooperates with three other RasGEFs - RasGEFB/M/U - to regulate spontaneous cell migration. We also found that RasGEFX and RasGEFB temporally and spatially regulate Ras activation and pseudopod formation for cell migration. In this colloquium, I will present the details of these findings.