Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?
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 approximately 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.
Beh
Christopher T
CT
Department of Molecular Biology & Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada. ctbeh@sfu.ca
Alfaro
Gabriel
G
Duamel
Giselle
G
Sullivan
David P
DP
Kersting
Michael C
MC
Dighe
Shubha
S
Kozminski
Keith G
KG
Menon
Anant K
AK
D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000098825:Oxysterol Binding Proteins
D002352:Carrier Proteins; C087901:KES1 protein, S cerevisiae; D008565:Membrane Proteins; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D000098825:Oxysterol Binding Proteins; D020741:rho GTP-Binding Proteins