Leptin (ob gene) of the South African clawed frog Xenopus laevis
Leptin (ob gene) of the South African clawed frog Xenopus laevis
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DOI：
10.1073/pnas.0507519103
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发表时间：
2006-06-27
影响因子：
11.1
通讯作者：
Denver, Robert J.
中科院分区：
文献类型：
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作者：
Crespi, Erica J.;Denver, Robert J.
瘦素是肥胖（ob）基因的蛋白质产物，是由脂肪分泌的I型细胞因子激素，其是食物摄取调节不可或缺的并且影响幼年和成年哺乳动物的几乎每个生理系统。自从1994年在老鼠中发现瘦素以来，生物学家一直在其他物种中寻找直链基因，但成功有限。本文报道了爪蟾瘦素及其受体的鉴定和功能研究。尽管与哺乳动物leptins的氨基酸序列相似性较低（约35%），但青蛙蛋白具有几乎相同的预测三级结构，并且可以在体外激活青蛙和小鼠LR。我们发现，重组青蛙瘦素（rxLeptin）是一个强大的免疫原在青蛙，因为它是在哺乳动物，但这种反应不会发展，直到midprometorphosis。然而，在早期prometamorphosis，外源rxLeptin诱导的生长和发展的后肢，LR mRNA的表达。rx瘦素也刺激细胞增殖培养的后肢从早期prometamorphic蝌蚪，测量[H-3]胸苷摄取。这些发现证明瘦素可以影响早期发育过程中的肢体生长和分化。此外，瘦素及其受体的分离和鉴定为阐明这种重要激素的结构和功能进化提供了必要的基础。
Leptin, the protein product of the obese (ob) gene, is a type-I cytokine hormone secreted by fat that is integral to food intake regulation and influences almost every physiological system in juvenile and adult mammals. Since the identification of leptin in the mouse in 1994, biologists have searched for orthologous genes in other species with limited success. In this article, we report the identification and functional characterization of leptin and leptin receptor (LR) in Xenopus. Despite low amino acid sequence similarity to mammalian leptins (approximate to 35%) the frog protein has a nearly identical predicted tertiary structure and can activate the frog and mouse LRs in vitro. We showed that recombinant frog leptin (rxLeptin) is a potent anorexigen in frogs, as it is in mammals, but this response does not develop until midprometamorphosis. However, during early prometamorphosis, exogenous rxLeptin induced growth and development of the hind limb, where LR mRNA is expressed. The rxLeptin also stimulated cell proliferation in cultured hind limbs from early prometamorphic tadpoles, as measured by [H-3]thymidine uptake. These findings are evidence that leptin can influence limb growth and differentiation during early development. Furthermore, the isolation and characterization of leptin and its receptor in a nonamniote provides an essential foundation for elucidating the structural and functional evolution of this important hormone.