Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity

Arupratan Das, Brian D. Slaughter, Jay R. Unruh, William D. Bradford, Richard Alexander, Boris Rubinstein, Rong Li

Research output: Contribution to journalArticle

Abstract

Lipid asymmetry at the plasma membrane is essential for such processes as cell polarity, cytokinesis and phagocytosis. Here we find that a lipid flippase complex, composed of Lem3, Dnf1 or Dnf2 (ref. ), has a role in the dynamic recycling of the Cdc42 GTPase, a key regulator of cell polarity, in yeast. By using quantitative microscopy methods, we show that the flippase complex is required for fast dissociation of Cdc42 from the polar cortex by the guanine nucleotide dissociation inhibitor. A loss of flippase activity, or pharmacological blockage of the inward flipping of phosphatidylethanolamine, a phospholipid with a neutral head group, disrupts Cdc42 polarity maintained by guanine nucleotide dissociation inhibitor-mediated recycling. Phosphatidylethanolamine flipping may reduce the charge interaction between a Cdc42 carboxy-terminal cationic region with the plasma membrane inner leaflet, enriched for the negatively charged lipid phosphatidylserine. Using a reconstituted system with supported lipid bilayers, we show that the relative composition of phosphatidylethanolamine versus phosphatidylserine directly modulates Cdc42 extraction from the membrane by guanine nucleotide dissociation inhibitor.

Original languageEnglish (US)
Pages (from-to)304-310
Number of pages7
JournalNature Cell Biology
Volume14
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

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Guanine Nucleotide Dissociation Inhibitors
Cell Polarity
Recycling
Phospholipids
Phosphatidylserines
Maintenance
Lipids
Cell Membrane
Cytophagocytosis
Cytokinesis
GTP Phosphohydrolases
Lipid Bilayers
Microscopy
Yeasts
Pharmacology
Membranes
phosphatidylethanolamine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Das, A., Slaughter, B. D., Unruh, J. R., Bradford, W. D., Alexander, R., Rubinstein, B., & Li, R. (2012). Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity. Nature Cell Biology, 14(3), 304-310. https://doi.org/10.1038/ncb2444

Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity. / Das, Arupratan; Slaughter, Brian D.; Unruh, Jay R.; Bradford, William D.; Alexander, Richard; Rubinstein, Boris; Li, Rong.

In: Nature Cell Biology, Vol. 14, No. 3, 03.2012, p. 304-310.

Research output: Contribution to journalArticle

Das, A, Slaughter, BD, Unruh, JR, Bradford, WD, Alexander, R, Rubinstein, B & Li, R 2012, 'Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity', Nature Cell Biology, vol. 14, no. 3, pp. 304-310. https://doi.org/10.1038/ncb2444
Das, Arupratan ; Slaughter, Brian D. ; Unruh, Jay R. ; Bradford, William D. ; Alexander, Richard ; Rubinstein, Boris ; Li, Rong. / Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity. In: Nature Cell Biology. 2012 ; Vol. 14, No. 3. pp. 304-310.
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