The Mevalonate Pathway Controls Heart Formation in Drosophila by Isoprenylation of Gγ1

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Science  01 Sep 2006:
Vol. 313, Issue 5791, pp. 1301-1303
DOI: 10.1126/science.1127704

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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 Gγ1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell–autonomous requirement of Gγ1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.

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