Author: ["Arupratan Das","Brian D. Slaughter","Jay R. Unruh","William D. Bradford","Richard Alexander","Boris Rubinstein","Rong Li"]
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Abstract
In budding yeast, polarized Cdc42 localization is supported in part by guanine nucleotide dissociation inhibitor (GDI)-mediated extraction from the plasma membrane. Li and colleagues now show that a lipid flippase complex containing Lem3 and Dnf1 or Dnf2 contributes to membrane lipid asymmetry to facilitate GDI-mediated extraction of Cdc42. Lipid asymmetry at the plasma membrane is essential for such processes as cell polarity, cytokinesis and phagocytosis1,2,3. Here we find that a lipid flippase complex, composed of Lem3, Dnf1 or Dnf2 (ref. 4), has a role in the dynamic recycling of the Cdc42 GTPase, a key regulator of cell polarity5, 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.Cite this article
Das, A., Slaughter, B., Unruh, J. et al. Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity. Nat Cell Biol 14, 304–310 (2012). https://doi.org/10.1038/ncb2444 