Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Elife. 2024 Jun 20;13:RP93662. doi: 10.7554/eLife.93662.
Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with its adaptor protein melanophilin (Mlph). Mlph contains four functional regions, including Rab27a-binding domain, Myo5a GTD-binding motif (GTBM), Myo5a exon F-binding domain (EFBD), and actin-binding domain (ABD). The association of Myo5a with Mlph is known to be mediated by two specific interactions: the interaction between the exon-F-encoded region of Myo5a and Mlph-EFBD and that between Myo5a-GTD and Mlph-GTBM. Here, we identify a third interaction between Myo5a and Mlph, that is, the interaction between the exon-G-encoded region of Myo5a and Mlph-ABD. The exon-G/ABD interaction is independent from the exon-F/EFBD interaction and is required for the association of Myo5a with melanosome. Moreover, we demonstrate that Mlph-ABD interacts with either the exon-G or actin filament, but cannot interact with both of them simultaneously. Based on above findings, we propose a new model for the Mlph-mediated Myo5a transportation of melanosomes.
黑素体在黑素细胞周边区域的运输和定位依赖于肌球蛋白-5a（Myo5a），它通过与衔接蛋白黑素瘤磷蛋白（Mlph）相互作用来结合黑素体。Mlph 包含四个功能区域，包括 Rab27a 结合域、Myo5a GTD 结合基序（GTBM）、Myo5a 外显子 F 结合域（EFBD）和肌动蛋白结合域（ABD）。已知 Myo5a 与 Mlph 的结合是由两个特定的相互作用介导的：Myo5a 外显子 F 编码区与 Mlph-EFBD 之间的相互作用，以及 Myo5a-GTD 与 Mlph-GTBM 之间的相互作用。在这里，我们确定了 Myo5a 与 Mlph 之间的第三种相互作用，即 Myo5a 外显子 G 编码区与 Mlph-ABD 之间的相互作用。外显子 G/ABD 相互作用独立于外显子 F/EFBD 相互作用，是 Myo5a 与黑素体结合所必需的。此外，我们证明 Mlph-ABD 与外显子 G 或肌动蛋白丝相互作用，但不能同时与两者相互作用。基于以上发现，我们提出了一个新的模型，用于解释 Mlph 介导的 Myo5a 运输黑素体的过程。
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