♦ See referenced article, J. Biol. Chem. 2013, 288, 18381–18391
Sphingosine 1-phosphate (S1P) is a bioactive lipid that has roles in both intracellular and extracellular signaling. The lipid is dephosphorylated in vitro by two phosphatases, sphingosine-1-phosphate phosphatases 1 and 2. The biological functions of these enzymes are not well defined. In this Paper of the Week, a team led by Richard L. Proia at the National Institute of Diabetes and Digestive and Kidney Diseases studied mice missing the gene for sphingosine-1-phosphate phosphatase 1. The mice looked normal at birth, but over the course of their first week of life, they suffered from stunted growth and peeling skin. Most died before weaning. The mutant mice surviving to adulthood had skin abnormalities. An analysis of their keratinocytes, the predominant cell type in the outermost layer of the skin, revealed that there was an overabundance of S1P. The authors concluded, “The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.”
Sgpp1−/− pups show skin abnormalities. A, mice at 0.5 days. B, mice 4 days after birth.