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

Christopher T. Beh*, Gabriel Alfaro, Giselle Duamel, David P. Sullivan, Michael C. Kersting, Shubha Dighe, Keith G. Kozminski, Anant K. Menon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9-13
Number of pages5
JournalMolecular and Cellular Biochemistry
Volume326
Issue number1-2
DOIs
StatePublished - 2009

Keywords

  • Cell polarization
  • Cholesterol
  • Nonvesicular sterol transport
  • OSH genes
  • Oxysterol-binding proteins
  • Rho small GTPases
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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