A dominant mutation in tyrp1A leads to melanophore death in zebrafish
A dominant mutation in tyrp1A leads to melanophore death in zebrafish
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DOI：
10.1111/pcmr.12272
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发表时间：
2014-09-01
影响因子：
4.3
通讯作者：
Irion, Uwe
中科院分区：
文献类型：
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作者：
Krauss, Jana;Geiger-Rudolph, Silke;Irion, Uwe
脊椎动物中黑色素的生物合成依赖于酪氨酸酶家族的三种酶的功能，酪氨酸酶（Tyr）、酪氨酸酶相关蛋白1（Tyrp 1）和多巴色素互变异构酶（Dct或Tyrp 2）。Tyrp 1可能在黑素细胞的存活和增殖中发挥额外的作用。在这里，我们描述了一个突变的tyrp 1A，其中两个tyrp 1旁系同源的斑马鱼，导致黑色素细胞死亡，导致半显性表型。这种突变是蛋白质氨基末端部分的Arg->Cys变化，类似于人类和小鼠的突变，它们分别导致金发（美拉尼西亚人）或黑发与白色碱基。我们证明了斑马鱼的表型取决于突变蛋白的存在和黑色素的合成。超微结构分析表明，突变体中黑素体的形态和色素含量发生了改变。这些结构变化可能是观察到的细胞死亡的根本原因，令人惊讶的是，这不会导致图案缺陷。
Melanin biosynthesis in vertebrates depends on the function of three enzymes of the tyrosinase family, tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and dopachrome tautomerase (Dct or Tyrp2). Tyrp1 might play an additional role in the survival and proliferation of melanocytes. Here, we describe a mutation in tyrp1A, one of the two tyrp1 paralogs in zebrafish, which causes melanophore death leading to a semi-dominant phenotype. The mutation, an Arg->Cys change in the amino-terminal part of the protein, is similar to mutations in humans and mice where they lead to blond hair (in melanesians) or dark hair with white bases, respectively. We demonstrate that the phenotype in zebrafish depends on the presence of the mutant protein and on melanin synthesis. Ultrastructural analysis shows that the melanosome morphology and pigment content are altered in the mutants. These structural changes might be the underlying cause for the observed cell death, which, surprisingly, does not result in patterning defects.