TY - JOUR
T1 - Yeast oxysterol-binding proteins
T2 - Sterol transporters or regulators of cell polarization?
AU - Beh, Christopher T.
AU - Alfaro, Gabriel
AU - Duamel, Giselle
AU - Sullivan, David P.
AU - Kersting, Michael C.
AU - Dighe, Shubha
AU - Kozminski, Keith G.
AU - Menon, Anant K.
N1 - Funding Information:
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.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Cell polarization
KW - Cholesterol
KW - Nonvesicular sterol transport
KW - OSH genes
KW - Oxysterol-binding proteins
KW - Rho small GTPases
KW - Saccharomyces cerevisiae
UR - http://www.scopus.com/inward/record.url?scp=67349144029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349144029&partnerID=8YFLogxK
U2 - 10.1007/s11010-008-9999-7
DO - 10.1007/s11010-008-9999-7
M3 - Article
C2 - 19125315
AN - SCOPUS:67349144029
SN - 0300-8177
VL - 326
SP - 9
EP - 13
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -