Acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation

Abstract

Internalization of macromolecules and membrane into cells through endocytosis is critical for cellular growth, signaling, and plasma membrane (PM) tension homeostasis. Although endocytosis is responsive to both biochemical and physical stimuli, how physical cues modulate endocytic pathways is less understood. In contrary to the accumulating discoveries on the effects of increased PM tension on endocytosis, less is known about how a decrease of PM tension impacts on membrane trafficking. Here we reveal that an acute decrease of PM tension results in phosphatidic acid (PA) production, F-actin and phosphatydil-4,5-bisphosphate (PI(4,5)P2)-enriched dorsal membrane ruffling and subsequent macropinocytosis in myoblasts. The PA production induced by decreased PM tension depends on phospholipase D2 (PLD2) activation via PLD2 nanodomain disintegration. Furthermore, the “decreased PM tension-PLD2-macropinocytosis” pathway is dominant in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway which converts acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P2 activities.