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.
Mattei
Sara
S
Laboratoire de Biochimie et Biophysique des Systemes Integres, DRDC/BBSI, UMR 5092 CNRS-CEA-UJF, CEA-Grenoble, 17 Rue des Martyrs, F-38054 Grenoble cedex 9, France.
Klein
Gérard
G
Satre
Michel
M
Aubry
Laurence
L
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
C511870:ALIX protein, Drosophila; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C097753:PDCD6 protein, human; D015800:Protozoan Proteins