Shaping the landscape: Metabolic regulation of S1P gradients

Sphingosine-1-phosphate (S1P) is a lipid that functions as a metabolic intermediate and a cellular signaling molecule. These roles are integrated when compartments with differing extracellular S1P concentrations are formed that serve to regulate functions within the immune and vascular systems, as well as during pathologic conditions. Gradients of S1P concentration are achieved by the organization of cells with specialized expression of S1P metabolic pathways within tissues. S1P concentration gradients underpin the ability of S1P signaling to regulate in vivo physiology. This review will discuss the mechanisms that are necessary for the formation and maintenance of S1P gradients, with the aim of understanding how a simple lipid controls complex physiology. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

► S1P is both a lipid metabolite and a signaling molecule.
► An S1P concentration gradient exists between circulation (high) and tissues (low).
► S1P gradients are produced by differential expression of metabolic pathways.
► S1P receptor signaling regulates normal physiology and pathogenesis.
► S1P gradients underlie the regulation of S1P receptor signaling.