The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1.
The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. A screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate, which causes loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.
Yi
Peng
P
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Han
Zhe
Z
Li
Xiumin
X
Olson
Eric N
EN
D020816:Amino Acid Motifs; D000818:Animals; D030801:Animals, Genetically Modified; D002448:Cell Adhesion; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000209:etiology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism*; D023421:Models, Animal; D009154:Mutation; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010496:Pericardium / Q000166:cytology; D017368:Protein Prenylation; D019076:Transgenes
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006903:Hydroxymethylglutaryl CoA Reductases; D019204:GTP-Binding Proteins; D008798:Mevalonic Acid