O-acetylation of Gd3 : An Enigmatic Modification Regulating Apoptosis?

Glycosphingolipids (GSLs) are amphipathic molecules with a polar glycan chain as a head group and a hydrophobic sphingosine-containing ceramide tail, which is typically embedded in the outer leaflet of the plasma membrane (1). GSLs are no longer thought to be mere physical components of the membrane. They often cluster in “glycosignaling domains” (GSDs; reference 2), sometimes along with other sphingolipids, glycosylphosphatidylinositol (GPI)-anchored proteins, and cholesterol, forming “lipid rafts” (3). These microdomains are thought to regulate signal transduction via cis interactions with signal transducer molecules. A GSL called Gd3 has recently been shown to be involved in Fas-mediated apoptosis in hematopoietic cells, causing the loss of mitochondrial potential and the release of apoptotic factors (for reviews, see references 4 and 5). In this issue, Malisan et al. (6) show that a naturally occurring modification of G...