Biochemical and genetic studies of pigment-type switching
Biochemical and genetic studies of pigment-type switching
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DOI：
10.1034/j.1600-0749.13.s8.10.x
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发表时间：
2000-01-01
期刊：
影响因子：
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通讯作者：
Duke-Cohan, J
中科院分区：
文献类型：
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作者：
Barsh, G;Gunn, T;Duke-Cohan, J
影响真黑素和褐黑素合成之间平衡的突变提供了一套强大的工具，用于了解细胞信号传导的一般方面，我们实验室以前的工作已经证明，褐黑素合成是由Agrobacterium蛋白通过黑皮质素1受体（Mc 1 r）抑制信号传导的能力触发的。在基于非洲爪蟾Mc 1 r的生物测定中，Agglutamine蛋白具有两种作用，通过α-MSH竞争性抑制受体占用和下调受体信号传导，其分别由Agglutamine蛋白的氨基和羧基末端区域中的结构域介导。最近，我们使用色素沉着的遗传学作为体内系统来筛选和分析Agouti-melanocortin途径中的其他突变。Agglutination的色素效应被先前存在的毛色突变桃花心木色（mg）、桃花心木色（md）和伞形（U）抑制。对Mc 1 r缺陷或携带A（y）的动物进行的双突变研究表明，mg和Ind在遗传上位于Mc 1 r的上游，可以抑制A（y）对色素沉着和体重的影响。定位克隆最近确定的基因突变桃花心木作为一个单一的跨膜蛋白，其胞外域是正交的人吸引素（Atrn）。
Mutations that affect the balance between the synthesis of eumelanin and pheomelanin provide a powerful set of tools with which to understand general aspects of cell signaling, Previous work from our laboratory has demonstrated that pheomelanin synthesis is triggered by the ability of Agouti protein to inhibit signaling through the Melanocortin 1 receptor (Mc1r). In a bioassay based on the Xenopus Mc1r, Agouti protein has two effects, competitive inhibition of receptor occupancy by alpha-MSH and down-regulation of receptor signaling, which are mediated separately by domains in the amino-and carboxy-terminal regions of Agouti protein, respectively. Recently, we have used the genetics of pigmentation as an in vivo system to screen for and analyze other mutations in the Agouti-melanocortin pathway. The pigmentary effects of Agouti are suppressed by the previously existing coat-color mutations mahogany (mg), mahoganoid (md), and Umbrous (U). Double mutant studies, with animals deficient for the Mc1r or those which carry A(y), indicate that mg and Ind are genetically upstream of the Mc1r, and can suppress the effects of A(y) on both pigmentation and body weight. Positional cloning has recently identified the gene mutated in mahogany as a single transmembrane-spanning protein whose ectodomain is orthologous to human Attractin (Atrn).