Sphingolipids in Cell Signaling: Their Function as Receptor Ligands, Second Messengers, and Raft Constituents

Sphingolipids have lately been recognized as important signaling molecules with an unexpected multitude of actions and mechanisms. While we are currently just uncovering the tip of the iceberg, the available data give us an unprecedented understanding of how membrane rearrangements translate into the generation of intracellular lipid signaling molecules and further into secreted bioactive lipids. Furthermore, new concepts such as the rheostat of sphingolipids show that fundamental principles in signaling also do apply to this class of molecules. The plethora of sphingolipids as well as sphingolipid modifying enzymes seem to comprise many novel, attractive, and pharmaceutically exploitable targets beyond sphingolipidoses, in applications ranging from autoimmune diseases and neurodegenerative conditions to cancer. In this review, we summarize the mechanistic triad of action of sphingolipids as membrane/raft components, intracellular signaling molecules and secreted mediators.