Sphingosine-1-phosphate lyase has a central role in the development of <i>Dictyostelium discoideum</i>

Abstract

Sphingosine-1-phosphate, a product of sphingomyelin degradation, is an important element of signal transduction pathways that regulate cell proliferation and cell death. We have demonstrated additional roles for sphingosine-1-phosphate in growth and multicellular development. The specific disruption in Dictyostelium discoideum of the sphingosine-1-phosphate lyase gene, which encodes the enzyme that catalyzes sphingosine-1-phosphate degradation, results in a mutant strain with aberrant morphogenesis, as well as an increase in viability during stationary phase. The absence of sphingosine-1-phosphate lyase affects multiple stages throughout development, including the cytoskeletal architecture of aggregating cells, the ability to form migrating slugs, and the control of cell type-specific gene expression and terminal spore differentiation. This pleiotropic effect, which is due to the loss of sphingosine-1-phosphate lyase, establishes sphingolipids as pivotal regulatory molecules in a wide range of processes in multicellular development.