Drink or drive: competition between macropinocytosis and cell migration

The cytoskeleton is utilized for a variety of cellular processes, including migration, endocytosis and adhesion. The required molecular components are often shared between different processes, but it is not well understood how the cells balance their use. We find that macropinocytosis and cell migration are negatively correlated. Heavy drinkers move only slowly and vice versa, fast cells do not take big gulps. Both processes are balanced by the lipid phosphatidylinositol 3,4,5-trisphosphate (PIP₃). Elevated PIP₃ signalling causes a shift towards macropinocytosis and inhibits motility by redirecting the SCAR/WAVE complex, a major nucleator of actin filaments. High resolution microscopy shows that patches with high levels of PIP₃ recruit SCAR/WAVE on their periphery, resulting in circular ruffle formation and engulfment. Results shed new light on the role of PIP₃, which is commonly thought to promote cell motility.