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Phosphatidylserine is polarized and required for proper Cdc42 localization and for development of cell polarity

Nature Cell Biology volume 13, pages 1424–1430 (2011)Cite this article

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Abstract

Polarity is key to the function of eukaryotic cells. On the establishment of a polarity axis, cells can vectorially target secretion, generating an asymmetric distribution of plasma membrane proteins. From Saccharomyces cerevisiae to mammals, the small GTPase Cdc42 is a pivotal regulator of polarity. We used a fluorescent probe to visualize the distribution of phosphatidylserine in live S. cerevisiae. Remarkably, phosphatidylserine was polarized in the plasma membrane, accumulating in bud necks, the bud cortex and the tips of mating projections. Polarization required vectorial delivery of phosphatidylserine-containing secretory vesicles, and phosphatidylserine was largely excluded from endocytic vesicles, contributing to its polarized retention. Mutants lacking phosphatidylserine synthase had impaired polarization of the Cdc42 complex, leading to a delay in bud emergence, and defective mating. The addition of lysophosphatidylserine resulted in resynthesis and polarization of phosphatidylserine, as well as repolarization of Cdc42. The results indicate that phosphatidylserine—and presumably its polarization—are required for optimal Cdc42 targeting and activation during cell division and mating.

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Figure 1: phosphatidylserine distribution in budding yeast.
Figure 2: Secretion is required for the polarized distribution of phosphatidylserine.
Figure 3: phosphatidylserine is excluded from newly formed endocytic vesicles and endocytic organelles.
Figure 4: phosphatidylserine is required for optimal Cdc42 location, activity and cell polarity.
Figure 5: Effects of phosphatidylserine repletion and phosphatidylethanolamine depletion on Cdc42 localization.

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Acknowledgements

We thank C. McMaster (Dalhousie University, Halifax, Canada), S. Emr (Cornell University, Ithaca, USA), H. Pelham (MRC-LMB, Cambridge, UK), T. Levine (UCL, London, UK), D. Johnson (University of Vermont, Burlington, USA), K. Tanaka (Hokkaido University, Hokkaido, Japan), R. Collins (Cornell University, Ithaca, USA), E. Bi (UPENN, Philadelphia, USA), R. Li (Stowers Institute for Medical Research, Kansas City, USA), F. Cross (Rockefeller University, New York, USA), W. Guo (UPENN, Philadelphia, USA), C. Burd (UPENN, Philadelphia, USA), B. Andrews (University of Toronto, Toronto, Canada) and C. Boone (University of Toronto, Toronto, Canada) for providing strains and plasmids. We also thank C. McMaster for his comments on the manuscript. This work was supported by Canadian Institutes of Health Research (CIHR) grants 7075 and MOP4665. G.D.F. is the recipient of a CIHR postdoctoral fellowship. S.G. is the present holder of the Pitblado Chair in Cell Biology.

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  1. Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

    Gregory D. Fairn & Sergio Grinstein

  2. Department of Biochemistry and Developmental Biology, Institute of Biomedicine, Haartmaninkatu 8, 00014 University of Helsinki, Finland

    Martin Hermansson & Pentti Somerharju

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G.D.F. and S.G. conceived the project and designed experiments; G.D.F. and M.H. carried out experiments; G.D.F., M.H., P.S. and S.G. analysed the data; G.D.F. and S.G. wrote the manuscript.

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Correspondence to Sergio Grinstein.

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Fairn, G., Hermansson, M., Somerharju, P. et al. Phosphatidylserine is polarized and required for proper Cdc42 localization and for development of cell polarity. Nat Cell Biol 13, 1424–1430 (2011). https://doi.org/10.1038/ncb2351

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