Slc45a2 and V-ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease
Slc45a2 and V-ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease
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DOI：
10.1111/pcmr.12053
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发表时间：
2013-03-01
影响因子：
4.3
通讯作者：
Geisler, Robert
中科院分区：
文献类型：
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作者：
Dooley, Christopher M.;Schwarz, Heinz;Geisler, Robert
我们在这里提出的位置克隆的斑马鱼白化病突变体，并显示受影响的基因编码Slc 45 a2。人类orthopathy基因先前已被证明与人类肤色变化有关，其中的突变与OCA 4疾病有关。通过对白化病等位基因和酪氨酸酶缺陷突变体桑迪中黑素体的超微结构分析，我们对Slc 45 a2在黑素产生中的作用增加了新的见解。为了进一步了解Slc 45 a2的作用及其与参与黑化的其他蛋白质的可能相互作用，我们进一步分析了V-ATPase作为黑素体酸化剂的作用。我们发现，通过V-ATPase的遗传和化学抑制，从而增加黑素体内部pH值，有可能挽救白化病黑素体的黑化潜力。
We present here the positional cloning of the Danio rerio albino mutant and show that the affected gene encodes Slc45a2. The human orthologous gene has previously been shown to be involved in human skin color variation, and mutations therein have been implicated in the disease OCA4. Through ultrastructural analysis of the melanosomes in albino alleles as well as the tyrosinase-deficient mutant sandy, we add new insights into the role of Slc45a2 in the production of melanin. To gain further understanding of the role of Slc45a2 and its possible interactions with other proteins involved in melanization, we further analyzed the role of the V-ATPase as a melanosomal acidifier. We show that it is possible to rescue the melanization potential of the albino melanosomes through genetic and chemical inhibition of V-ATPase, thereby increasing internal melanosome pH.