B07 - Intracellular targets of sphingosine-1-phosphate and sphingosine: cross-regulation of cholesterol homeostasis

The project addresses the intracellular activities and targets of sphingosine-1-phosphate (S1P) in models of S1P lyase (Sgpl1) deficiency. We observed similarities in the phenotype of Sgpl1 deficiency and Niemann-Pick disease type C. The investigations focus on NPC1/2 proteins as interface between intracellular S1P/sphingosine and cholesterol homeostasis, regulation of the amyloid precursor protein by S1P in non-neuronal cells, and the phenotype of lysosomal lipid accumulation with enhanced Ca2+ storage. Ongoing studies with a photoaffinity label will be continued. The results shall help to understand the phenotype of Sgpl1-deficient mice and of patients with Sgpl1 mutations.

Links:

• Institute of General Pharmacology and Toxicology