Reverse fountain flow of phosphatidylinositol‐3,4‐bisphosphate polarizes migrating cells
Abstract
The ability of cells to polarize and move toward external stimuli plays a crucial role in development, as well as in normal and pathological physiology. Migrating cells maintain dynamic complementary distributions of Ras activity and of the phospholipid phosphatidylinositol‐3,4‐bisphosphate (PI(3,4)P2). Here, we show that lagging‐edge component PI(3,4)P2 also localizes to retracting leading‐edge protrusions and nascent macropinosomes, even in the absence of phosphatidylinositol 3,4,5‐trisphosphate (PIP3). Once internalized, macropinosomes break up into smaller PI(3,4)P2‐enriched vesicles, which fuse with the plasma membrane at the rear of the cell. Subsequently, the phosphoinositide diffuses toward the front of the cell, where it is degraded. Computational modeling confirms that this cycle gives rise to stable back‐to‐front gradient. These results uncover a surprising “reverse‐fountain flow” of PI(3,4)P2 that regulates polarity.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 15, 2021
- Source ID
- 10.15252/embj.2020105094
Entities
People
- Debojyoti Biswas
- Dhiman Sankar Pal
- Pablo A. Iglesias
- Peter N. Devreotes
- Xiaoguang Li
Organizations
- Air Force Office of Scientific Research
- Defense Advanced Research Projects Agency
- Johns Hopkins University
- National Institutes of Health