Macropinocytosis is an endocytic pathway for rapid nutrient uptake. It is triggered by biochemical stimulation and executed through plasma membrane ruffling and actin polymerization. This leads to the formation of a large endocytic vacuole for the engulfment and internalization of solutes. It has been established that changes in plasma membrane (PM) tension influence endocytosis, but how this contributes to macropinocytosis is still unclear. Now, Ya-Wen Liu and colleagues (Loh et al., 2019) identify a signalling pathway that induces micropinocytosis upon a decrease in PM tension. The authors find that decreased membrane tension leads to the disintegration of phospholipase D2 (PLD2) membrane nanodomains and PLD2-dependent production of phosphatidic acid. This lipid is central to actin polymerization and membrane trafficking and the authors observe an enrichment of actin and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] at membrane ruffles, which form after PM tension decreases. These events lead to micropinocytosis in myotubes, and the authors find that this tension-mediated signalling axis is the pronounced pathway for these cells to induce macropinocytosis. In summary, this work describes the molecular basis for a PM tension-induced mechanotransduction pathway that leads to macropinocytosis.
