Highlights d Dyn2 promotes the maturation and turnover of podosomes d The actin-bundling activity of Dyn2 is regulated by Srcmediated phosphorylation d Centronuclear myopathy-linked Dyn2 mutants display abnormal actin-organizing activities

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. 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 phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P 2 ]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 prominent in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway that converts an acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P 2 -mediated processes.

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Neuromuscular junctions (NMJs) govern rapid and efficient neuronal communication with muscle cells, which relies on the proper architecture of specialized postsynaptic compartments. However, the intrinsic mechanism in muscle cells contributing to elaborate NMJ development has been unclear. In this study, we reveal that the GTPase dynamin-2 (Dyn2), bestknown for catalyzing synaptic vesicle endocytosis at the presynaptic membrane, is also involved in postsynaptic morphogenesis. We demonstrate that Dyn2 is enriched in the postsynaptic membrane of muscle cells and is involved in the maturation of neurotransmitter receptor clusters via its actin bundling ability. Dyn2 functions as a molecular girdle to regulate synaptic podosome turnover and promote morphogenesis of the postsynaptic apparatus. In Drosophila NMJs, Dyn2 is required to organize the postsynaptic actin cytoskeleton and to mediate its electrophysiological activities. Mechanistically, the actin binding, self-assembly, GTP hydrolysis ability, and Y597 phosphorylation of Dyn2 all regulate its actin bundling activity. Together, our study uncovers a role for Dyn2 in cytoskeleton remodeling and organization at the postsynaptic membrane of NMJs.