| 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. |
