Trafficking and developmental signaling: Alix at the crossroads

Alix is a phylogenetically conserved protein that participates in mammals in programmed cell death in association with ALG-2, a penta-EF-hand calciprotein. It contains an N-terminal Bro1 domain, a coiled-coil region and a C-terminal proline-rich domain containing several SH3- and WW-binding sites that contribute to its scaffolding properties. Recent data showed that by virtue of its Bro1 domain, Alix is functionally associated to the ESCRT complexes involved in the biogenesis of the multivesicular body and sorting of transmembrane proteins within this specific endosomal compartment. In Dictyostelium, an alx null strain shows a markedly perturbed starvation-induced morphogenetic program while ALG-2 disruptants remain unaffected. This review summarizes Dictyostelium data on Alix and ALG-2 homologues and evaluates whether known functions of Alix in other organisms can account for the developmental arrest of the alx null mutant and how Dictyostelium studies can substantiate the current understanding of the function(s) of this versatile and conserved signaling molecule.