A universal model for macropinocytosis and organizing large actin structures

Macropinocytosis is an ancient and highly conserved endocytic pathway that allows cells to take up large volumes of extracellular fluid. This plays several important roles such as allowing both protists and cancer cells to feed on extracellular proteins and enabling immune cells to sample the environment for antigens. Although many key components have been identified, the underlying mechanisms behind fluid engulfment remain mysterious, largely due to the complex highly variable and apparently disorganised nature of the large actin-based ruffles that drive uptake.

I will present a new biophysical-based model for the formation, closure and scission of macropinocytic structures, that we propose provides a universal mechanism for fluid engulfment across cell types. I will also provide evidence that the excitable small GTPase and phosphoinositide signalling network responsible for macropinocytosis provides a general mechanism for cells to generate the large actin structures that drive both migration and phagocytosis, and speculate on the evolutionary basis of Ras-driven cancer.