Rom2-dependent phosphorylation of Elo2 controls the abundance of very long-chain fatty acids

J Biol Chem. 2015 Feb 13;290(7):4238-47. doi: 10.1074/jbc.M114.629279. Epub 2014 Dec 17.

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.

Keywords: Fatty Acid; Fatty Acid Metabolism; Phosphoproteomics; Phosphorylation; Sphingolipid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism*
  • Cell Membrane / metabolism*
  • Fatty Acids / metabolism*
  • Gas Chromatography-Mass Spectrometry
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Homeostasis
  • Lipid Metabolism
  • Membrane Proteins / metabolism*
  • Phosphorylation
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Sphingolipids / metabolism*

Substances

  • Fatty Acids
  • Guanine Nucleotide Exchange Factors
  • Membrane Proteins
  • ROM2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sphingolipids
  • Acetyltransferases
  • ELO2 protein, S cerevisiae