title: Rom2-dependent phosphorylation of Elo2 controls the abundance of very long-chain fatty acids.
abstract: Sphingolipids are essential components of eukaryotic membranes, where they serve to maintain membrane integrity. They are important components of membrane trafficking and function in signaling as messenger molecules. Sphingolipids are synthesized de novo from very long-chain fatty acids (VLCFA) and sphingoid long-chain bases, which are amide linked to form ceramide and further processed by addition of various headgroups. Little is known concerning the regulation of VLCFA levels and how cells coordinate their synthesis with the availability of long-chain bases for sphingolipid synthesis. Here we show that Elo2, a key enzyme of VLCFA synthesis, is controlled by signaling of the guanine nucleotide exchange factor Rom2, initiating at the plasma membrane. This pathway controls Elo2 phosphorylation state and VLCFA synthesis. Our data identify a regulatory mechanism for coordinating VLCFA synthesis with sphingolipid metabolism and link signal transduction pathways from the plasma membrane to the regulation of lipids for membrane homeostasis.
authors.affiliation: From the Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, the Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06150.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Olson
authors.affiliation: From the Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115.
authors.forename: Florian
authors.initials: F
authors.lastname: Fröhlich
authors.affiliation: From the Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115.
authors.forename: Romain
authors.initials: R
authors.lastname: Christiano
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Southern Denmark, 0230 Odense, Denmark.
authors.forename: Hans K
authors.initials: HK
authors.lastname: Hannibal-Bach
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Southern Denmark, 0230 Odense, Denmark.
authors.forename: Christer S
authors.initials: CS
authors.lastname: Ejsing
authors.affiliation: From the Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142 twalther@hsph.harvard.edu.
authors.forename: Tobias C
authors.initials: TC
authors.lastname: Walther
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006706:Homeostasis; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C490929:ROM2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D000123:Acetyltransferases; C107118:ELO2 protein, S cerevisiae
keywords: Fatty Acid; Fatty Acid Metabolism; Phosphoproteomics; Phosphorylation; Sphingolipid