Macropinocytosis: Molecular mechanisms and regulation

Macropinocytosis is a conserved pathway for non-selective bulk uptake of extracellular fluid. It plays important roles in various cellular processes, including nutrient acquisition in Dictyostelium and cancer cells and antigen sampling by immune cells. This process is initiated by localized actin polymerization, which drives the formation of membrane protrusions that close to generate macropinosomes. Once formed, macropinosomes undergo maturation and traffic through the endolysosomal system for cargo degradation, whereas non-degradable material is exocytosed. Recent studies have uncovered conserved regulatory networks controlling macropinosome formation and maturation. This review provides an overview of these pathways, highlighting key molecular regulators and their coordinated responses to environmental signals. We also examine the interplay between macropinocytosis and cell migration, discussing potential mechanisms that balance these processes to optimize cellular function.