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Originally published as MBC in Press, 10.1091/mbc.E07-08-0806 on February 20, 2008

Vol. 19, Issue 5, 1922-1931, May 2008

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The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry

Mika Ikeda*, Akio Kihara*, Aki Denpoh*, and Yasuyuki Igarashi*,{dagger}

*Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; and {dagger}Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Sciences, Hokkaido University, Sapporo 001-0021, Japan

Submitted August 19, 2007; Revised January 8, 2008; Accepted February 7, 2008
Monitoring Editor: Sean Munro

Biological membranes consist of lipid bilayers. The lipid compositions between the two leaflets of the plasma membrane differ, generating lipid asymmetry. Maintenance of proper lipid asymmetry is physiologically quite important, and its collapse induces several cellular responses including apoptosis and platelet coagulation. Thus, a change in lipid asymmetry must be restored to maintain "lipid asymmetry homeostasis." However, to date no lipid asymmetry-sensing proteins or any related downstream signaling pathways have been identified. We recently demonstrated that expression of the putative yeast sphingoid long-chain base transporter/translocase Rsb1 is induced when glycerophospholipid asymmetry is altered. Using mutant screening, we determined that the pH-responsive Rim101 pathway, the protein kinase Mck1, and the transcription factor Mot3 all act in lipid asymmetry signaling, and that the Rim101 pathway was activated in response to a change in lipid asymmetry. The activated transcription factor Rim101 induces Rsb1 expression via repression of another transcription repressor, Nrg1. Changes in lipid asymmetry are accompanied by cell surface exposure of negatively charged phospholipids; we speculate that the Rim101 pathway recognizes the surface charges.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-08-0806) on February 20, 2008.

Address correspondence to: Akio Kihara (kihara{at}pharm.hokudai.ac.jp)

Abbreviations used: Endo H, endoglycosidase H; ESCRT, endosomal sorting complex required for transport; HA, hemagglutinin; NRE, Nrg1-responsive element; PC, phosphatidylcholine; PE, phosphatidylethanolamine; Pgk1, phosphoglycerokinase 1; PI, phosphatidylinositol; PS, phosphatidylserine; Ro, Ro 09-0198; SC, synthetic complete; SM, sphingomyelin.






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