Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates
Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates
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DOI：
10.1095/biolreprod.107.066266
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发表时间：
2008-10-01
影响因子：
3.6
通讯作者：
Levavi-Sivan, Berta
中科院分区：
文献类型：
--
作者：
Biran, Jakob;Ben-Dor, Shifra;Levavi-Sivan, Berta
KISS1基因编码kisspeptin神经肽，激活KISS1受体（KISS1R； G蛋白偶联受体54；GPR54），参与GnRH分泌的神经内分泌调节。为了研究KISS1的生理功能和进化保守性，我们克隆了负鼠、非洲爪蟾和斑马鱼的KISS1 cdna。加工斑马鱼、非洲爪蟾或负鼠的KISS蛋白将分别释放一个含有52、54或53个氨基酸残基的羧基末端修饰肽。所有已知的脊椎动物KISS1肽的系统发育分析显示，根据典型的脊椎动物分类，这些序列具有明显的聚类性。斑马鱼的kiss1基因由两个外显子和一个内含子组成。对从斑马鱼大脑中克隆的两个kissiR进行实时PCR分析，发现kiss1， kiss1ra和kiss1rb的表达，其中kiss1ra与其他鱼类kiss1受体更相似，在性腺中高度表达，而kiss1rb在其他非脑组织中表达。雌性kiss1 mRNA水平在生命的最初几周逐渐增加，在卵巢含有成熟卵母细胞的鱼类中达到峰值，而雄性kiss1 mRNA水平在受精后6周达到峰值，此时睾丸处于精子发生的初始阶段，在青春期后下降。斑马鱼的kiss1ra和kiss1rb在两性中表达方式相似，但存在差异。这些结果表明，Kiss1/Kiss1r系统也可能参与鱼类的青春期启动。与人类的KISS1R一样，Kiss1ra通过PKC途径转导其活性，而Kiss1rb通过PKC和PKA途径转导其活性。人类KISS1R受体被huKISS10amide和zfKISS10amide高度激活，而斑马鱼的两种KISS1R受体类型对酰胺的敏感性较低。
The KISS1 gene encodes the kisspeptin neuropeptide, which activates the KISS1 receptor (KISS1R; G protein-coupled receptor 54; GPR54) and participates in neuroendocrine regulation of GnRH secretion. To study the physiological function(s) and evolutionary conservation of KISS1, we cloned opossum, Xenopus, and zebrafish kiss1 cDNAs. Processing zebrafish, Xenopus, or opossum KISS proteins would liberate a carboxy-terminal amidated peptide with 52, 54, or 53 amino acid residues, respectively. Phylogenetic analysis of all known vertebrate KISS1 peptides showed clear clustering of the sequences according to canonical vertebrate classes. The zebrafish kiss1 gene consists of two exons and one intron. Real-time PCR analysis of two kissiR cloned from zebrafish brain found expression of kiss1, kiss1ra, and kiss1rb, with kiss1ra-more similar to other piscine Kiss1 receptors-highly expressed in the gonads and kiss1rb in other nonbrain tissues. In females kiss1 mRNA levels gradually increased during the first few weeks of life to peak in fish with ovaries containing mature oocytes, while in males kiss1 mRNA levels peaked after 6 wk postfertilization when the testes exhibited initial stages of spermatogenesis and decreased after puberty. Zebrafish kiss1ra and kiss1rb were expressed differentially with similar patterns in both genders. These results indicate that the Kiss1/Kiss1r system may participate in puberty initiation in fish as well. Like human KISS1R, Kiss1ra transduces its activity via the PKC pathway, whereas Kiss1rb does so via both PKC and PKA pathways. The human KISS1R was highly activated by both huKISS10amide and zfKISS10amide, whereas both zebrafish Kiss1 receptor types were less sensitive to amidation.