P10 - AG Levkau Nadine Thomas

Trafficking of sphingosine-1-phosphate (S1P) between membranes and high-density lipoproteins as crucial component of S1P signalling and lipid transfer

High-density lipoproteins (HDL) are the most potent endogenous factors that protect against atherosclerosis-related cardiovascular diseases by taking up cholesterol from peripheral tissues and eliminating it via billiary excretion. It is known that biological effects of HDL can be partially or entirely attributed to their Sphingosine-1-phosphate content. Sphingosine-1-phosphate (S1P) is a bioactive, signalling sphingolipid.

It could be shown that this S1P levels are lower in HDL particles from patients with coronary artery disease. But at the present state it is still unknown which influence cholesterol has on the transport of the sphingolipids and vice versa.

Furthermore it is still unknown how and under which physicochemical and molecular conditions the transfer of S1P / sphingosine takes place in the cell.

The aim of this project is to determine the transport kinetics and dynamics of the sphingolipids S1P and sphingosine. Both the intermembrane transfer of S1P / sphingosine and the transport of cholesterol to HDL under the presence of S1P / Sphingosine will be investigated.