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Updated: Jan 21, 2026
Determination of Plasma Membrane Partitioning for Peripherally-associated Proteins
Published on: June 15, 2018
An acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation
Julie Loh1, Mei-Chun Chuang1, Shan-Shan Lin1
1Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
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)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 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)P2-mediated processes.
Insights
A decrease in plasma membrane tension triggers phosphatidic acid production and macropinocytosis in cells. This newly identified pathway involves phospholipase D2 and is crucial for maintaining cell membrane homeostasis.
Area of Science:
- Cell Biology
- Biophysics
- Mechanobiology
Background:
- Endocytosis is vital for cellular functions, responding to biochemical and physical cues.
- While increased plasma membrane tension effects on endocytosis are known, the impact of decreased tension is less understood.
Purpose of the Study:
- To investigate how a decrease in plasma membrane tension influences cellular membrane trafficking and endocytic pathways.
Main Methods:
- Studied myoblasts and myotubes to observe cellular responses to acute decreases in plasma membrane tension.
- Utilized biochemical assays and microscopy to analyze phosphatidic acid production, F-actin dynamics, and PI(4,5)P2 localization.
Main Results:
- An acute decrease in plasma membrane tension induced phosphatidic acid production, F-actin, and PI(4,5)P2-enriched membrane ruffling and macropinocytosis.
- Phosphatidic acid production was dependent on phospholipase D2 activation.
- This pathway was prominent in myotubes, suggesting a role in muscle cell homeostasis.
Conclusions:
- Identified a novel mechanotransduction pathway linking decreased plasma membrane tension to macropinocytosis via phosphatidic acid production.
- This pathway is mediated by phospholipase D2, F-actin, and PI(4,5)P2, contributing to plasma membrane tension homeostasis.
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