Insulin-like signaling and the neural circuit for integrative behavior in C-elegans
Insulin-like signaling and the neural circuit for integrative behavior in C-elegans
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DOI：
10.1101/gad.1479906
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发表时间：
2006-11-01
影响因子：
10.5
通讯作者：
Mori, Ikue
中科院分区：
文献类型：
--
作者：
Kodama, Eiji;Kuhara, Atsushi;Mori, Ikue
秀丽隐杆线虫表现出与食物相关的行为，该行为受过去的培养温度调节。 INS-1（人胰岛素同源物）的突变导致了这种整合行为的缺陷。 DAF-2/胰岛素受体和AGE-1/磷脂酰肌醇3 (PI-3)激酶的突变部分抑制了ins-1突变体的缺陷，而叉头型转录因子DAF-16的突变导致了微弱的缺陷。此外，分泌蛋白HEN-1的突变显示出与INS-1的协同作用。 AGE-1 在三个中间神经元（AIY、AIZ 或 RIA）中的任何一个中表达，挽救了 Age-1 突变体的缺陷特征。钙成像显示饥饿诱导 INS-1 介导的 AIZ 活性下调。我们的结果表明，INS-1 与 HEN-1 合作，拮抗 DAF-2 胰岛素样信号通路，以调节食物相关整合行为所需的中间神经元活动。
Caenorhabditis elegans exhibits a food-associated behavior that is modulated by the past cultivation temperature. Mutations in INS-1, the homolog of human insulin, caused the defect in this integrative behavior. Mutations in DAF-2/insulin receptor and AGE-1/phosphatidylinositol 3 (PI-3)-kinase partially suppressed the defect of ins-1 mutants, and a mutation in DAF-16, a forkhead-type transcriptional factor, caused a weak defect. In addition, mutations in the secretory protein HEN-1 showed synergistic effects with INS-1. Expression of AGE-1 in any of the three interneurons, AIY, AIZ, or RIA, rescued the defect characteristic of age-1 mutants. Calcium imaging revealed that starvation induced INS-1-mediated down-regulation of AIZ activity. Our results suggest that INS-1, in cooperation with HEN-1, antagonizes the DAF-2 insulin-like signaling pathway to modulate interneuron activity required for food-associated integrative behavior.