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Rab7 and Rab27a control two motor protein activities involved in melanosomal transport

机译：Rab7和Rab27a控制参与黑色素体转运的两种运动蛋白活性

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摘要

Melanosomes are lysosome-related organelles that synthesize, store and transport melanin. In epidermal melanocytes, melanosomes mature and are transferred to surrounding keratinocytes, which is essential for skin and coat colour. Mouse coat colour mutants reveal a critical role for the small GTPase Rab27a, which recruits myosin Va through its effector protein melanophilin/Slac2a. Here we have studied how two different Rab GTPases control two motor proteins during subsequent phases in transport of melanosomes. We show that the small GTPase Rab7 mainly associates with early and intermediate stage melanosomes and Rab27a to intermediate and mature melanosomes. Rab27a is found in an active state on mature melanosomes in the tips of the dendrites. The Rab7-Rab7-interacting lysosomal protein-dynein pathway only controls early and intermediate stage melanosomes because the mature melanosomes lack Rab7 and associate with the actin network through Rab27a recruited MyoVa. Thus two Rab proteins regulate two different motor proteins, thereby controlling complementary phases in melanosome biogenesis: Rab7 controls microtubule-mediated transport of early and Rab27a the subsequent actin-dependent transport of mature melanosomes.
机译：黑素体是与溶酶体有关的细胞器，可合成，储存和运输黑色素。在表皮黑素细胞中，黑素体成熟并转移到周围的角质形成细胞中，这对于皮肤和毛色是必不可少的。小鼠皮毛颜色突变体揭示了小GTPase Rab27a的关键作用，Rab27a通过其效应蛋白黑色素/ Slac2a募集了肌球蛋白Va。在这里，我们研究了两种不同的Rab GTPases在黑素体运输的后续阶段如何控制两种运动蛋白。我们显示，小的GTPase Rab7主要与早期和中期的黑素体相关，而Rab27a与中间和成熟的黑素体相关。在树突尖端的成熟黑素体上发现Rab27a处于活性状态。 Rab7-Rab7相互作用的溶酶体蛋白-动力蛋白途径仅控制早期和中期的黑素体，因为成熟的黑素体缺乏Rab7，并且通过Rab27a募集的MyoVa与肌动蛋白网络结合。因此，两种Rab蛋白调节两种不同的运动蛋白，从而控制黑素体生物发生中的互补相：Rab7控制微管介导的早期黑素体转运，而Rab27a控制随后的肌动蛋白依赖性成熟黑素体转运。

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