Reverse fountain flow of phosphatidylinositol-3,4-bisphosphate polarizes migrating cells

Xiaoguang Li, Dhiman Sankar Pal, Debojyoti Biswas, Pablo A. Iglesias, Peter N. Devreotes

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere105094
JournalEMBO Journal
Issue number4
StatePublished - Feb 15 2021


  • cell migration
  • excitability
  • membrane flow
  • neutrophils
  • refractory period

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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