Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans
Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans
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DOI：
10.1073/pnas.0809881106
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发表时间：
2009-02-03
影响因子：
11.1
通讯作者：
Schoofs, Liliane
中科院分区：
文献类型：
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作者：
Lindemans, Marleen;Liu, Feng;Schoofs, Liliane
在哺乳动物中，下丘脑促性腺激素释放激素（GnRH）是一种神经肽，刺激促性腺激素从垂体前叶释放。在原口类无脊椎动物中是否存在一个假定的生殖轴功能等价物一直是一个有争议的问题。在这项研究中，GnRH受体在线虫线虫（Ce-GnRHR）的配体发现使用生物信息学方法。该肽及其前体使人联想到昆虫脂肪运动激素和来自被囊动物和高等脊椎动物的GnRH-前激素原前体。我们克隆了AKH-GnRH-like preprohormone和Ce-GnRHR，并在HEK 293 T细胞中表达了GPCR。GnRHR由C. elegans AKH-GnRH-like peptide（EC 50 = 150 nM）和果蝇AKH和我们在EST数据库中发现的其他线虫AKH-GnRH。与昆虫AKH受体和脊椎动物GnRH受体信号传导类似，Ce-AKH-GnRH通过G α（q）蛋白以Ca 2+作为第二信使激活其受体。Ce-GnRH HR、Ce-AKH-GnRH或两者的基因沉默导致产卵过程延迟，与缺乏正常剂量GnRH肽或具有突变的GnRH前体或受体基因的哺乳动物青春期延迟相当。目前的数据支持这样的观点，AKH-GnRH信号系统可能出现在后生动物进化的早期，其在生殖中的作用可能已经开发的protostomians和deuterostomians分歧之前。
In mammals, hypothalamic gonadotropin-releasing hormone (GnRH) is a neuropeptide that stimulates the release of gonadotropins from the anterior pituitary. The existence of a putative functional equivalent of this reproduction axis in protostomian invertebrates has been a matter of debate. In this study, the ligand for the GnRH receptor in the nematode Caenorhabditis elegans (Ce-GnRHR) was found using a bioinformatics approach. The peptide and its precursor are reminiscent of both insect adipokinetic hormones and GnRH-preprohormone precursors from tunicates and higher vertebrates. We cloned the AKH-GnRH-like preprohormone and the Ce-GnRHR and expressed the GPCR in HEK293T cells. The GnRHR was activated by the C. elegans AKH-GnRH-like peptide (EC50 = 150 nM) and by Drosophila AKH and other nematode AKH-GnRHs that we found in EST databases. Analogous to both insect AKH receptor and vertebrate GnRH receptor signaling, Ce-AKH-GnRH activated its receptor through a G alpha(q) protein with Ca2+ as a second messenger. Gene silencing of Ce-GnRHR, Ce-AKH-GnRH, or both resulted in a delay in the egg-laying process, comparable to a delay in puberty in mammals lacking a normal dose of GnRH peptide or with a mutated GnRH precursor or receptor gene. The present data support the view that the AKH-GnRH signaling system probably arose very early in metazoan evolution and that its role in reproduction might have been developed before the divergence of protostomians and deuterostomians.