A biochemical function for attractin in agouti-induced pigmentation and obesity
A biochemical function for attractin in agouti-induced pigmentation and obesity
复制标题
DOI：
10.1038/83741
复制
发表时间：
2001-01-01
期刊：
影响因子：
30.8
通讯作者：
Barsh, GS
中科院分区：
文献类型：
--
作者：
He, L;Gunn, TM;Barsh, GS
刺豚鼠蛋白是一种旁分泌信号分子，通常仅限于皮肤，在致死性黄色 (A(y)) 小鼠中异位表达，并通过模仿主要存在于下丘脑的刺豚鼠相关蛋白 (Agrp) 导致肥胖。小鼠吸引素 (Atrn) 是一种广泛表达的跨膜蛋白，其在桃花心木 (Atrn(mg-3J)/Atrn(mg-3J)) 突变小鼠中的功能丧失会阻断 A(y) 的多效性作用。在这里，我们在转基因、生化和遗传相互作用实验中证明，在体外和体内，吸引素是agouti蛋白的低亲和力受体，但不是Agrp。 Atrn(mg-3J)/Atrn(mg-3J) 小鼠的其他组织病理学异常和跨物种基因组比较表明，从生理学和进化的角度来看，Atrn 具有多种功能。
Agouti protein, a paracrine signaling molecule normally limited to skin, is ectopically expressed in lethal yellow (A(y)) mice, and causes obesity by mimicking agouti-related protein (Agrp), found primarily in the hypothalamus. Mouse attractin (Atrn) is a widely expressed transmembrane protein whose loss of function in mahogany (Atrn(mg-3J)/Atrn(mg-3J)) mutant mice blocks the pleiotropic effects of A(y). Here we demonstrate in transgenic, biochemical and genetic-interaction experiments that attractin is a low-affinity receptor for agouti protein, but not Agrp, in vitro and in vivo. Additional histopathologic abnormalities in Atrn(mg-3J)/Atrn(mg-3J) mice and cross-species genomic comparisons indicate that Atrn has multiple functions distinct from both a physiologic and an evolutionary perspective.