Regulation of yellow pigment formation in mice: A historical perspective
Regulation of yellow pigment formation in mice: A historical perspective
复制标题
DOI：
10.1034/j.1600-0749.2003.00012.x
复制
发表时间：
2003-02-01
期刊：
影响因子：
--
通讯作者：
Wolff, GL
中科院分区：
文献类型：
--
作者：
Wolff, GL
毛囊黑素细胞的色素合成受到大量的环境和遗传因素的调节，其中许多因素在本文中进行了讨论。真黑素（非黄色）色素由毛囊黑素细胞在α-黑素细胞刺激激素与黑皮质素受体1结合后产生。这种激素与黑素细胞膜的结合被琼脂糖蛋白信号蛋白（ASP）阻断，该蛋白由琼脂糖蛋白基因座编码，并导致合成黄色色素，而不是非黄色（黑色/棕色）色素。毛囊细胞周期性释放ASP导致黑色/棕色毛发，并带有近顶端黄色带。这是许多哺乳动物的野生型毛色模式，被称为agglomerus。逆转录转座子样脑池内A颗粒诱导的小鼠agglutinin基因位点的几个显性突变导致ASP异位过度表达，并且动物具有更高比例的全黄毛。ASP在基本上所有体细胞中的这种异常存在导致“黄色肥胖小鼠综合征”。肥胖与ASP与黑皮质素受体4的结合有关，黑皮质素受体4使后者失活。该综合征还包括高胰岛素血症、增加的躯体生长和增加的对增生和癌变的易感性。这些综合征组分的生理和分子基础尚未阐明。这一历史性的审查细分，在适用的情况下，到1992年之前和之后的小节，强调的agglutinase和延伸位点及其蛋白质产物的克隆的影响，对识别的分子和生理途径调制的多方面的pheomelanogenesis。
Pigment synthesis by hair follicle melanocytes is modulated by a large number of environmental and genetic factors, many of which are discussed in this review. Eumelanic (non-yellow) pigment is produced by hair follicle melanocytes following the binding of alpha-melanocyte stimulating hormone to melanocortin receptor 1. Binding of this hormone to the melanocyte membrane is blocked by agouti signaling protein (ASP) which is encoded by the agouti locus and results in the synthesis of yellow pigment, instead of non-yellow (black/brown) pigment. The cyclical release of ASP by hair follicle cells results in a black/brown hair with a subapical yellow band. This is the wild-type coat color pattern of many mammals and is called agouti. Several dominant mutations at the agouti locus in mice, induced by retrotransposon-like intracisternal A particles, result in ectopic over-expression of ASP and animals with much higher proportions of all-yellow hairs. This abnormal presence of ASP in essentially all body cells results in the 'yellow agouti obese mouse syndrome.' The obesity has been associated with binding of ASP to melanocortin receptor 4 inactivating the latter. The syndrome also includes hyperinsulinemia, increased somatic growth, and increased susceptibility to hyperplasia and carcinogenesis. The physiologic and molecular bases for these syndrome components have not yet been elucidated. This historically orientated review is subdivided, where applicable, into pre- and post-1992 subsections to emphasize the impact of the cloning of the agouti and extension loci and their protein products on the identification of the molecular and physiological pathways modulating the manifold aspects of pheomelanogenesis.