Both insulin and calcium channel signaling are required for developmental regulation of serotonin synthesis in the chemosensory ADF neurons of Caenorhabditis elegans
Both insulin and calcium channel signaling are required for developmental regulation of serotonin synthesis in the chemosensory ADF neurons of Caenorhabditis elegans
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DOI：
10.1016/j.ydbio.2006.06.005
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发表时间：
2006-10-01
影响因子：
2.7
通讯作者：
Estevez, Miguel
中科院分区：
文献类型：
--
作者：
Estevez, Annette O.;Cowie, Robin H.;Estevez, Miguel
适当的钙通道和胰岛素信号传导对正常的大脑发育至关重要。P/Q型电压门控钙通道Cacna 1a突变的瘦小鼠发生小脑萎缩，同源人类基因突变与偏头痛和癫痫倾向增加有关。类似地，胰岛素信号传导的异常与异常的大脑生长和偏头痛倾向有关。以前，我们已经表明，在ADF化学感觉神经元的秀丽隐杆线虫LfNC-2/Ca 2+通道功能影响TGF-β依赖的发育调节色氨酸水解酶，限速酶在5-羟色胺合成。在这里，我们表明，dqf-2/胰岛素受体中的功能降低突变同样会降低色氨酸羟化酶：：CFP报告基因构建体的发育表达。在daf-2和unc-2突变体背景中观察到的色氨酸羟化酶表达的降低在遗传上可被daf-16/叉头转录因子（一种β 2/胰岛素受体的效应物）的功能降低突变抑制，或被5-羟色胺受体拮抗剂赛庚啶抑制。总的来说，这些数据表明，在发育调节中需要的β-16和雷公藤红素依赖性抑制色氨酸水解酶表达的β-2和β-2的功能。(c)2006年爱思唯尔公司All rights reserved.
Proper calcium channel and insulin signaling are essential for normal brain development. Leaner mice with a mutation in the P/Q-type voltage-gated calcium channel, Cacna1a, develop cerebellar atrophy and mutations in the homologous human gene are associated with increased migraine and seizure tendency. Similarly, abnormalities in insulin signaling are associated with abnormal brain growth and migraine tendency. Previously, we have shown that in the ADF chemosensory neurons of Caenorhahditis elegans LfNC-2/Ca2+ channel function affects TGF-beta-dependent developmental regulation of tryptophan hydroaylase, the rate-limiting enzyme in serotonin synthesis. Here we show that developmental expression of a tryptophan hydroxylase: :CFP reporter construct is similarly decreased by reduction-of-function mutations in the dqf-2/insulin receptor. This decreased expression of tryptophan hydroxylase observed in both the daf-2 and unc-2 mutant backgrounds is suppressible either genetically by reduction-of-function mutations in the daf-16/forkhead transcription factor, an effector of the DAF-2/insulin receptor, or pharmacologically by the serotonin receptor antagonist cyproheptadine. Overall, these data suggest that both UNC-2 and DAF-2 function are required in the developmental regulation of DAF-16 and serotonin-dependent inhibition of triptophan hydrosylase expression. (c) 2006 Elsevier Inc. All rights reserved.