Macropinosomen

Macropinosomen, also called macropinosomes, are large endocytic vesicles formed during macropinocytosis, a fluid-phase uptake pathway in many animal cells. They arise when actin-driven membrane ruffles at the cell surface fold back onto the plasma membrane, enclosing extracellular fluid and solutes to create spherical vesicles that can range from several hundred nanometers up to a few micrometers in diameter. Unlike receptor-mediated endocytosis, macropinocytosis is relatively non-specific and is often stimulated by growth factors or cellular stress.

Formation and regulation of macropinosomen formation depend on signaling cascades that promote actin remodeling. Key players include Rac1 and other small GTPases, PI3K signaling, and actin-nucleating factors that drive membrane ruffling. The process results in the scission and internalization of the newly formed vesicle, which then enters the endocytic pathway. Macropinosomen contents are typically delivered to early endosomes, with maturation proceeding to late endosomes and lysosomes; some traffic can involve recycling routes back to the plasma membrane. The internal pH becomes acidic as cargo is processed.

Functions and significance vary by cell type. In immune cells such as macrophages and dendritic cells, macropinosomen uptake supports antigen sampling and presentation. In cancer, certain tumor cells increase macropinocytosis to obtain nutrients, including extracellular proteins, supporting rapid growth. Pathogens can exploit this pathway to gain entry. Macropinosomen are distinguished from phagosomes by their size, non-specific cargo uptake, and reliance on actin-driven membrane ruffles rather than receptor-mediated uptake. Researchers often track fluid-phase tracers like dextran to study their formation and trafficking.