A hormonal signaling pathway influencing C-elegans metabolism, reproductive development, and life span
A hormonal signaling pathway influencing C-elegans metabolism, reproductive development, and life span
复制标题
DOI：
10.1016/s1534-5807(01)00085-5
复制
发表时间：
2001-12-01
影响因子：
11.8
通讯作者：
Antebi, A
中科院分区：
文献类型：
--
作者：
Gerisch, B;Weitzel, C;Antebi, A
在秀丽隐杆线虫发育过程中，动物必须根据感官提示在生殖生长或滞育之间进行选择。胰岛素/IGF-I 和 TGF-β 信号传导在孤儿核受体 daf-12 上汇聚来介导这种选择。在这里，我们表明 daf-9 作用于这些输入的下游，但作用于 daf-12 的上游。 daf-9 和 daf-12 突变体具有相似的幼虫缺陷，并调节胰岛素/IGF-I 和性腺信号，从而调节成年寿命。 daf-9 编码与脊椎动物类固醇生成羟化酶相关的细胞色素 P450，表明它可以代谢 DAF-12 配体。甾醇可能是 daf-9 底物和 daf-12 配体，因为胆固醇剥夺表型突变缺陷。表达 daf-9 的感觉神经元、皮下组织和体细胞性腺细胞可识别潜在的内分泌组织。显然，亲脂性激素影响线虫的代谢、滞育和寿命。
During C. elegans development, animals must choose between reproductive growth or dauer diapause in response to sensory cues. Insulin/IGF-I and TGF-beta signaling converge on the orphan nuclear receptor daf-12 to mediate this choice. Here we show that daf-9 acts downstream of these inputs but upstream of daf-12. daf-9 and daf-12 mutants have similar larval defects and modulate insulin/IGF-I and gonadal signals that regulate adult life span. daf-9 encodes a cytochrome P450 related to vertebrate steroidogenic hydroxylases, suggesting that it could metabolize a DAF-12 ligand. Sterols may be the daf-9 substrate and daf-12 ligand because cholesterol deprivation phenocopies mutant defects. Sensory neurons, hypodermis, and somatic gonadal cells expressing daf-9 identify potential endocrine tissues. Evidently, lipophilic hormones influence nematode metabolism, diapause, and life span.