Molecular mechanism of intracellular and in vivo function of an anorexic peptide, Nesfatin-1

在目前的研究中，我们探索了下丘脑厌食激素Nesfatin-1(NAP-1)的细胞内信号通路。放射受体分析表明，NAP-1特异性受体定位于小鼠下丘脑和小鼠神经母细胞瘤NB41A3细胞的细胞膜。NAP-1通过MAP激酶和L型钙通道增加细胞内cAMP反应元件结合蛋白(CREB)的磷酸化。此外，在胰岛β细胞中，NAP-1采用了与中枢神经系统不同的信号通路。我们发现了NAP-1受体的候选基因(GPCRn)，并建立了GPCRn缺陷小鼠(GPCRnKO)。

In the current study, we explored the intracellular signaling pathway of a hypothalamic anorexic hormone, Nesfatin-1 (NAP-1). Radioreceptor assays indicated that NAP-1 specific receptor should be located in the cell membrane fraction of mouse hypothalamus and of NB41A3 cells, which derived from mouse neuroblastoma. Through MAP kinase and L-type calcium channel, NAP-1 increased intracellular phosphorylation of cAMP response element binding protein (CREB). Moreover, it was revealed that in pancreatic beta cells, NAP-1 employed a distinct signaling pathway from that in central nervous system. We identified a candidate gene (GPCRn) for NAP-1 specific receptor and established GPCRn deficient mice (GPCRnKO).