It was also proposed that it could play a key role in late apoptotic mitochondria-mediated events, i.e. the release form this organelle of apoptogenic factors such as cytochrome c. In this scenario we RO 48-8071 fumarate hypothesized that lipid rafts constituents, normally localized mainly at the cell surface and able to engulf a series of molecules of importance in the cell suicide process, can proceed from the cell Tinidazole plasma membrane to the mitochondria via a microtubule-dependent mechanism. Microtubules may be used as tracks to direct intracytoplasmic transport of lipid raft glycosphingolipid to mitochondria. This was demonstrated by the observed association of GD3 with tubulin and by the experiments previously carried out by inhibiting microtubule polymerization. Under these experimental conditions, the trafficking of GD3 molecule towards mitochondria appeared to be impaired. However, the fact that the integrity of microtubules is mandatory for GD3 association to tubulin is still puzzling. This question remains to be elucidated and some insight may come from the studies carried out in this paper in which we analyzed the microtubule associated protein CLIPR-59. In fact, CLIPR-59, in addition to its microtubule binding, has recently been shown to be associated with lipid rafts by a double palmitoylation on tandem cysteines within the C-terminal domain. Since CLIPR-59 is associated not only with the plasma membrane, but is also targeted to trans Golgi network membranes, it may regulate both plasma membrane and trans Golgi network interactions via microtubules. Here, in addition, we demonstrated, by FRET, that CLIPR-59 is also capable of directly interacting with lipid raft-associated GD3. Interestingly, it was proposed that CLIPR-59 binds microtubules only when already localized to its membrane target. It can therefore be hypothesized that it can play a role either as cytoplasmic linker between lipid rafts and microtubules or to locally destabilize the assembly of microtubules close to lipid rafts. More in general, according to CLIP model, CLIPR-59 would establish an interaction between cell membranes and microtubules, thus regulating membrane dynamics. In particular, CLIPR-59 may facilitate rafts/microtubules interaction following anti-CD95/Fas treatment.