The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Gγ1
The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Gγ1
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DOI：
10.1126/science.1127704
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发表时间：
2006-09-01
期刊：
影响因子：
56.9
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Yi, Peng;Han, Zhe;Olson, Eric N.
参与心脏形成的早期形态发生机制在进化上是保守的。对控制果蝇心脏发育的基因进行的筛选显示，存在心脏缺陷，其中心包和心肌细胞解离，导致心脏功能丧失和胚胎死亡。这种表型是由编码HMG-CoA还原酶、甲羟戊酸途径中的下游酶和G蛋白G γ 1的基因突变引起的，G蛋白G γ 1是香叶基香叶基化的，因此代表类异戊二烯生物合成的终点。我们的研究结果揭示了心脏形成的G γ 1香叶基香叶基化的胰岛细胞自主需求，并建议参与甲羟戊酸途径在先天性心脏病。
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 G gamma 1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of G gamma 1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.