Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C-elegans insulin gene family
Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C-elegans insulin gene family
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DOI：
10.1101/gad.867301
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发表时间：
2001-03-15
影响因子：
10.5
通讯作者：
Ruvkun, G
中科院分区：
文献类型：
--
作者：
Pierce, SB;Costa, M;Ruvkun, G
DAF-2胰岛素样受体的活性是秀丽线虫生殖生长和正常成虫寿命所必需的。信息学分析确定了37个线虫基因，预计将编码胰岛素样肽。这些基因中有许多是不同的胰岛素超家族成员，而且许多是聚集的，这表明该家族最近出现了多样化。INS基因主要在神经元中表达，包括感觉神经元，其中一部分是生殖发育所必需的。哺乳动物胰岛素的结构预测和可能的C肽裂解位点表明，INS-1与胰岛素关系最密切。INS-1的过表达或在INS-1调控序列控制下的人胰岛素的表达，导致部分穿透性停滞在Dauer阶段，并增强弱daf-2突变体的Dauer停滞，表明INS-1和人胰岛素拮抗DAF-2胰岛素样信号。INS-1编码区的缺失不会增强或抑制Dauer停滞，这表明37个INS基因之间存在功能冗余。在测试的其他五个INS基因中，唯一另一个含有预测的C肽的INS基因也能拮抗daf-e信号，而四个没有C肽的INS基因不能，这表明INS家族内功能的多样性。
The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-e signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.