Genetic Evidence for Function of the bHLH-PAS Protein Gce/Met As a Juvenile Hormone Receptor.
Genetic Evidence for Function of the bHLH-PAS Protein Gce/Met As a Juvenile Hormone Receptor.
复制标题
DOI：
10.1371/journal.pgen.1005394
复制
发表时间：
2015-07
期刊：
影响因子：
4.5
通讯作者：
Hill RJ
中科院分区：
文献类型：
--
作者：
Jindra M;Uhlirova M;Charles JP;Smykal V;Hill RJ
保幼激素（JH）在控制昆虫和其他节肢动物的发育和繁殖中起着重要作用。合成的类似JH的化合物如甲氧普烯被用作对抗重要的农业、家庭和病媒害虫的有效杀虫剂。然而，JH及其杀虫模拟物的受体介导作用长期以来一直是争议的主题。bHLH-PAS耐甲氧普仑蛋白（Met），沿着其果蝇寄生生殖细胞表达的（Gce），已经成为主要的JH受体候选者，但是缺少该蛋白必须结合JH以实现其在正常昆虫发育中的作用的关键证据。在这里，我们表明，GCE结合天然D。黑腹菌JH、其前体法尼酸甲酯和一些合成JH模拟物。在这种配体结合的条件下，Gce介导JH依赖的基因表达和激素在苍蝇发育过程中的重要作用。配体结合口袋中阻止JH与蛋白质结合的三个不同的单氨基酸突变中的任何一个都阻断了这些功能。只有能够结合JH的转基因Gce才能恢复D.黑腹果蝇Met无效突变体和缺乏Gce和Met的果蝇中的拯救生存力，否则这些果蝇将在化蛹时死亡。类似地，Gce和Met的缺失可以通过表达野生型而非突变的转基因D. Met蛋白。这一遗传证据明确确立了Gce/Met在JH受体中的作用，从而解决了节肢动物生物学中一个长期存在的问题。保幼激素（JH）在节肢动物的发展中起着至关重要的作用，包括海洋动物生物量的一半和超过一百万种昆虫，对生态系统，农业（传粉者和害虫）和人类健康（疾病媒介）产生巨大影响。尽管经过几十年的研究，这些独特的倍半萜类激素的受体仍然难以捉摸。在这里，我们提供了明确的遗传学证据，建立在昆虫发育过程中的Gce/Met蛋白的基本生物学功能是关键依赖于其结合JH的能力，在功能上有效地定义了JH受体。JH受体的明确鉴定对我们理解节肢动物生物学具有深远的意义。它还为开发环境友好、更安全的杀虫剂定义了分子靶点。
Juvenile hormones (JHs) play a major role in controlling development and reproduction in insects and other arthropods. Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural, household and disease vector pests. However, a receptor mediating effects of JH and its insecticidal mimics has long been the subject of controversy. The bHLH-PAS protein Methoprene-tolerant (Met), along with its Drosophila melanogaster paralog germ cell-expressed (Gce), has emerged as a prime JH receptor candidate, but critical evidence that this protein must bind JH to fulfill its role in normal insect development has been missing. Here, we show that Gce binds a native D. melanogaster JH, its precursor methyl farnesoate, and some synthetic JH mimics. Conditional on this ligand binding, Gce mediates JH-dependent gene expression and the hormone's vital role during development of the fly. Any one of three different single amino acid mutations in the ligand-binding pocket that prevent binding of JH to the protein block these functions. Only transgenic Gce capable of binding JH can restore sensitivity to JH mimics in D. melanogaster Met-null mutants and rescue viability in flies lacking both Gce and Met that would otherwise die at pupation. Similarly, the absence of Gce and Met can be compensated by expression of wild-type but not mutated transgenic D. melanogaster Met protein. This genetic evidence definitively establishes Gce/Met in a JH receptor role, thus resolving a long-standing question in arthropod biology. Juvenile hormones (JHs) play critical roles in the development of arthropods, comprising half the animal biomass of the oceans and over a million insect species, which have an enormous impact on ecosystems, agriculture (pollinators and pests) and health of mankind (disease vectors). Despite decades of research, a receptor for these unique sesquiterpenoid hormones has remained elusive. Here, we provide definitive genetic evidence establishing that the essential biological function of the Gce/Met protein during insect development is critically dependent on its ability to bind JH, in effect functionally defining a JH receptor. Unequivocal identification of a JH receptor has profound implications for our understanding of arthropod biology. It also defines a molecular target for development of environmentally friendly, safer insecticides.
登录
查看更多内容
影响因子：
4.1
作者：
Li M;Liu P;Wiley JD;Ojani R;Bevan DR;Li J;Zhu J
通讯作者：
Zhu J
保幼激素受体复合物作用于Mcm4和Mcm7促进飞蝗多倍体和卵黄发生
影响因子：
4.5
作者：
Guo W;Wu Z;Song J;Jiang F;Wang Z;Deng S;Walker VK;Zhou S
通讯作者：
Zhou S
DOI：
10.1668/0003-1569(2001)041
发表时间：
2001-04-01
期刊：
AMERICAN ZOOLOGIST
影响因子：
--
作者：
Kramer, DL;McLaughlin, RL
通讯作者：
McLaughlin, RL
DOI：
10.1073/pnas.1116123109
发表时间：
2011-12-27
影响因子：
11.1
作者：
Charles, Jean-Philippe;Iwema, Thomas;Jindra, Marek
通讯作者：
Jindra, Marek
DOI：
10.1073/pnas.94.25.13499
发表时间：
1997-12-09
影响因子：
11.1
作者：
Jones, G;Sharp, PA
通讯作者：
Sharp, PA