Neurokinin Bs and neurokinin B receptors in zebrafish-potential role in controlling fish reproduction

Neurokinin Bs and neurokinin B receptors in zebrafish-potential role in controlling fish reproduction
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DOI:
10.1073/pnas.1119165109
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发表时间:
2012-06-26
影响因子:
11.1
通讯作者:
Levavi-Sivan, Berta
Levavi-Sivan, Berta
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Biran, Jakob;Palevitch, Ori;Levavi-Sivan, Berta

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脊椎动物生殖的内分泌调节是通过包括速激肽在内的多种肽类神经激素的协同作用来实现的。为了研究神经激肽B(NKB)的进化保守性和生理功能,我们从多种鱼类中鉴定了速激肽(tac)和tac受体(NKBR)基因,并从斑马鱼中克隆了两种cDNA。系统发育分析表明,鱼类Tac 3s和哺乳动物神经激肽基因来自一个谱系。在编码NKB的区域中发现不同鱼类之间的高度同一性;所有共享共同的C-末端序列。虽然鱼Tac 3基因编码两个推定的速激肽肽,哺乳动物的直系同源物编码只有一个。第二种鱼类推定肽,称为神经激肽F(NKF),是独特的,并发现在计算机测试时在鱼类物种中是保守的。Tac 3a在胚胎的缰核中不对称地表达,而在成年斑马鱼中,表达Tac 3a的神经元定位于已知参与生殖的特定脑核中。斑马鱼tac 3a mRNA水平在生命的最初几周逐渐增加,并在青春期达到峰值。雌激素处理的青春期前的鱼引起的tac 3a,kiss 1,kiss 2和kiss 1 ra的表达增加。合成的斑马鱼肽(NKBa、NKBb和NKF)在体外通过PKC/Ca 2+和PKA/cAMP信号转导途径激活Tac 3受体。此外,单次腹腔注射NKBa和NKF显着增加成熟雌性斑马鱼的促黄体生成激素水平。这些结果表明,NKB/NKBR系统可能参与鱼类生殖的神经内分泌调控。
The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of several peptide neurohormones, tachykinin among them. To study the evolutionary conservation and physiological functions of neurokinin B (NKB), we identified tachykinin (tac) and tac receptor (NKBR) genes from many fish species, and cloned two cDNA forms from zebrafish. Phylogenetic analysis showed that piscine Tac3s and mammalian neurokinin genes arise from one lineage. High identity was found among different fish species in the region encoding the NKB; all shared the common C-terminal sequence. Although the piscine Tac3 gene encodes for two putative tachykinin peptides, the mammalian ortholog encodes for only one. The second fish putative peptide, referred to as neurokinin F (NKF), is unique and found to be conserved among the fish species when tested in silico. tac3a was expressed asymmetrically in the habenula of embryos, whereas in adults zebrafish tac3a-expressing neurons were localized in specific brain nuclei that are known to be involved in reproduction. Zebrafish tac3a mRNA levels gradually increased during the first few weeks of life and peaked at pubescence. Estrogen treatment of prepubertal fish elicited increases in tac3a, kiss1, kiss2, and kiss1ra expression. The synthetic zebrafish peptides (NKBa, NKBb, and NKF) activated Tac3 receptors via both PKC/Ca2+ and PKA/cAMP signal-transduction pathways in vitro. Moreover, a single intraperitoneal injection of NKBa and NKF significantly increased leuteinizing hormone levels in mature female zebrafish. These results suggest that the NKB/NKBR system may participate in neuroendocrine control of fish reproduction.