Department of Animal Sciences, The Ohio State University, Columbus, OH, USA.
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Commun Biol. 2024 May 17;7(1):592. doi: 10.1038/s42003-024-06284-5.
Limited studies using animal models with a few natural mutations in melanophilin (Mlph) provided partial functions of Mlph in melanosome trafficking. To investigate cellular functions of Mlph, especially ZnF motif of Mlph, we analyzed all three Mlph knockout (KO) quail lines, one and two base pair (bp) deletions as models for total KO, and three bp deletion causing deletion of one Cysteine (C84del) in the ZnF motif. All quail lines had diluted feather pigmentation with impaired dendritogenesis and melanosome transport in melanocytes. In vitro studies revealed capability of binding of the ZnF motif to PIP3, and impairment of PI3P binding and mislocalization of MLPH proteins with ZnF motif mutations. The shortened melanocyte dendrites by the C84del mutation were rescued by introducing WT Mlph in vitro. These results revealed the diluted feather pigmentation by Mlph mutations resulted from congregation of melanosomes in the cell bodies with impairment of the dendritogenesis and the transport of melanosomes to the cell periphery.
有限的使用带有少数天然突变黑色素瘤转移相关蛋白（Mlph）的动物模型的研究提供了 Mlph 在黑素小体运输中的部分功能。为了研究 Mlph 的细胞功能，特别是 Mlph 的 ZnF 结构域，我们分析了所有三种 Mlph 敲除（KO）鹌鹑系，一个和两个碱基对（bp）缺失作为完全 KO 的模型，以及三个 bp 缺失导致 ZnF 结构域中一个半胱氨酸（C84del）缺失。所有鹌鹑系均表现出羽毛色素稀释，树突生成受损和黑素细胞中黑素小体运输受损。体外研究表明 ZnF 结构域与 PIP3 的结合能力，以及 PI3P 结合的损害和 ZnF 结构域突变导致 MLPH 蛋白的定位错误。用 C84del 突变缩短的黑素细胞树突在体外引入 WT Mlph 后得到挽救。这些结果表明，Mlph 突变导致的羽毛色素稀释是由于黑素小体在细胞体中聚集，树突生成和黑素小体向细胞边缘的运输受损所致。
