An 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. 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.

Complimentary action of structured and unstructured domains of epsin supports clathrin-mediated endocytosis at high tension

“…The IDP domain provides binding to AP2 and clathrin, which is required for epsin's ability to stabilize CCSs, since ENTH domain alone is cytosolic. Our finding is significant as most membrane-associated proteins disassemble or dissociate from the lipid bilayer as membrane tension increases 22,35,41 . The complementary actions of ENTH and IDP domains of epsin enable it to detect membrane tension variations to support the flat-to-dome transition in high tension environments.…”

“…The tension response by epsin to changes in resting tension or acute tension variation is unique from other membrane-associated proteins. Typically, elevated tension reduces the recruitment of proteins to the membrane 22,35 . Paradoxically, epsin shows an increase of recruitment in response to elevated tension.…”

Endomembranes: Unsung Heroes of Mechanobiology?

“…There appears to be a strong connection between the endo/lysosomal system and membrane tension (King et al, 2020;López-Hernández et al, 2020;Mercier et al, 2020). An increase in the PM tension is balanced by the exocytosis of a subpopulation of recycling endosomes (Gauthier et al, 2009) while a burst of endocytosis occurs when the PM tension decreases (Shi and Baumgart, 2015;Loh et al, 2019). Additionally, endosomes play a fundamental role in the adaptation of the cell to osmotic stress, situation where the cell confronts itself with ionic imbalance, leading in turn to water influx or efflux and volume changes (Figure 2).…”

Amyloid-β induced membrane damage instigates tunneling nanotubes by exploiting p21-activated kinase dependent actin remodulation

“…Involvement of the clathrin-and dynamin-independent endocytosis is also relevant in maintaining cellular homeostasis by regulating membrane stress and cell surface expansion (Apodaca, 2017;Thottacherry et al, 2018). Recent study reported that induced macropinocytosis could be the cause of decreased plasma membrane stress (Loh et al, 2019). Exocytosis is involved in the expansion of cell surface area and results in decreased membrane stress.…”