macropinocytosis

Macropinocytosis is a form of endocytosis in which cells take up extracellular fluid and solutes through large, actin-driven plasma membrane protrusions that enclose fluid-filled vesicles called macropinosomes. This process is clathrin- and caveolin-independent and is driven by extensive actin remodeling and membrane ruffling, rather than the selective cargo recognition seen in other endocytic pathways.

During macropinocytosis, growth factors or certain pathogens stimulate the formation of ruffles on the cell surface. These ruffles fold back onto the plasma membrane and seal to form macropinosomes, which are typically large, ranging from about 0.2 to 5 micrometers in diameter. The cargo is largely nonspecific, encompassing extracellular fluid, nutrients, proteins, lipids, and even some microbes. In immune cells such as dendritic cells and macrophages, macropinocytosis contributes to antigen sampling and surveillance.

Macropinosomes mature and traffic through the endocytic system, often fusing with early and late endosomes and eventually lysosomes where their contents can be degraded. Some macropinosomes recycle membrane components back to the surface. The process is regulated by signaling pathways involving PI3K, Rac1, Cdc42, and PAK1, which coordinate actin dynamics and vesicle formation. Pharmacological inhibitors that block macropinocytosis, such as amiloride derivatives (for example, EIPA), are commonly used in experimental settings to dissect the pathway.

Physiologically, macropinocytosis supports nutrient uptake in certain cancer cells, particularly those with Ras-driven signaling. It also serves in immune function by enabling antigen uptake, while several viruses and bacteria can exploit macropinocytosis to gain cellular entry.