The mode of ceramide action: the alkyl chain protrusion model.

Ceramides can induce cellular differentiation, activation, survival and apoptosis and thus appear capable of changing the life style of virtually any cell type. Ceramides have been shown to play important roles in a variety of signal transduction systems. Within the last few years much has been learnt about the biology of ceramide, yet we understand little about the molecular mode of ceramide action. To reconcile the plethora of published functional data with the biochemical properties of ceramide, a model is proposed in which the alkyl chain of ceramide interacts with a hydrophobic cavity of a signalling protein. This model implies that ceramide, through protrusion of an alkyl chain, provides a lipid anchor to recruit proteins to membranes. The topology and kinetics of ceramide production by sphingomyelinases may thus play a pivotal role in the inducible compartmentalization and activation of signal transduction complexes.