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Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?

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Abstract

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) are a conserved family of soluble cytoplasmic proteins that can bind sterols, translocate between membrane compartments, and affect sterol trafficking. These properties make ORPs attractive candidates for lipid transfer proteins (LTPs) that directly mediate nonvesicular sterol transfer to the plasma membrane. To test whether yeast ORPs (the Osh proteins) are sterol LTPs, we studied endoplasmic reticulum (ER)-to-plasma membrane (PM) sterol transport in OSH deletion mutants lacking one, several, or all Osh proteins. In conditional OSH mutants, ER-PM ergosterol transport slowed ~20-fold compared with cells expressing a full complement of Osh proteins. Although this initial finding suggested that Osh proteins act as sterol LTPs, the situation is far more complex. Osh proteins have established roles in Rho small GTPase signaling. Osh proteins reinforce cell polarization and they specifically affect the localization of proteins involved in polarized cell growth such as septins, and the GTPases Cdc42p, Rho1p, and Sec4p. In addition, Osh proteins are required for a specific pathway of polarized secretion to sites of membrane growth, suggesting that this is how Osh proteins affect Cdc42p- and Rho1p-dependent polarization. Our findings suggest that Osh proteins integrate sterol trafficking and sterol-dependent cell signaling with the control of cell polarization.

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Abbreviations

ER:

Endoplasmic reticulum

GFP:

Green-fluorescent protein

LTP:

Lipid transfer protein

ORP:

Oxysterol-binding protein related protein

OSBP:

Oxysterol-binding protein

PM:

Plasma membrane

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Acknowledgments

Research funding is provided to Christopher T. Beh by a grant from The Natural Science and Engineering Research Council of Canada (NSERC) and by joint contributions from the Canadian Foundation for Innovation and the British Columbia Knowledge and Development Fund. K.G.K. was funded by a grant (#0723342) from the National Science Foundation.

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Authors and Affiliations

  1. Department of Molecular Biology & Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada

    Christopher T. Beh, Gabriel Alfaro & Giselle Duamel

  2. Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA

    David P. Sullivan, Michael C. Kersting & Anant K. Menon

  3. Departments of Biology & Cell Biology, University of Virginia, Charlottesville, VA, 22904, USA

    Shubha Dighe & Keith G. Kozminski

Authors
  1. Christopher T. Beh
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  2. Gabriel Alfaro
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  3. Giselle Duamel
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  4. David P. Sullivan
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  5. Michael C. Kersting
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  6. Shubha Dighe
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  7. Keith G. Kozminski
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  8. Anant K. Menon
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Correspondence to Christopher T. Beh.

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Beh, C.T., Alfaro, G., Duamel, G. et al. Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?. Mol Cell Biochem 326, 9–13 (2009). https://doi.org/10.1007/s11010-008-9999-7

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  • DOI: https://doi.org/10.1007/s11010-008-9999-7

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