Abstract
Macropinocytosis is a unique pathway of endocytosis characterised by the nonspecific internalisation of large amounts of extracellular fluid, solutes and membrane in large endocytic vesicles known as macropinosomes. Macropinocytosis is important in a range of physiological processes, including antigen presentation, nutrient sensing, recycling of plasma proteins, migration and signalling. It has become apparent in recent years from the study of specialised cells that there are multiple pathways of macropinocytosis utilised by different cell types, and some of these pathways are triggered by different stimuli. Understanding the physiological function of macropinocytosis requires knowledge of the regulation and fate of the macropinocytosis pathways in a range of cell types. Here, we compare the mechanisms of macropinocytosis in different primary and immortalised cells, identify the gaps in knowledge in the field and discuss the potential approaches to analyse the function of macropinocytosis in vivo.
Highlights
Endocytosis is a process carried out by eukaryotic cells that facilitates the internalisation of extracellular molecules and plasma membrane components
Macropinocytosis has only recently attracted attention in mainstream biology, Warren Lewis first described the morphological characteristics of this pathway in the 1930s, when he showed that macrophages and cancer cells ruffle and internalise extracellular fluid [7,8]
Macropinocytosis is critical to an ever-growing number of cellular processes, including but not limited to antigen presentation, signalling, nutrient acquisition, nutrient sensing and pathogen invasion
Summary
Endocytosis is a process carried out by eukaryotic cells that facilitates the internalisation of extracellular molecules and plasma membrane components. Macropinocytosis is one of the nonspecific endocytic pathways that has gained considerable recent attention, as this pathway has the unique property of rapidly internalising very large amounts of plasma membrane and extracellular fluid and functions in a range of physiological processes including nutrient uptake and nutrient sensing, signalling, antigen presentation and cell migration [2,3,4,5]. As macropinocytosis is the most efficient way for cells to internalise large amounts of extracellular fluid and plasma membrane, this pathway has a significant impact on the physiology of these cells. Perhaps not surprisingly, (micro)pinocytosis has been shown to make a significant contribution to the uptake of smaller 3 kDa dextran [19] These limitations in the specificity of fluid-phase markers for macropinocytosis highlight the need to identify macropinosome-specific molecules. As amiloride and its analogues have effects on other cellular processes, they cannot be considered specific inhibitors of macropinocytosis [31]
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