Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p150Glued complex in melanocytes
Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p150Glued complex in melanocytes
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DOI：
10.1242/jcs.094185
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发表时间：
2012-03-15
影响因子：
4
通讯作者：
Fukuda, Mitsunori
中科院分区：
文献类型：
--
作者：
Ohbayashi, Norihiko;Maruta, Yuto;Fukuda, Mitsunori
Melanoregulin （Mreg）是稀释抑制基因的产物，与哺乳动物表皮黑素细胞中黑素小体运输的调节有关，因为在rab27a缺乏的黑素细胞中，Mreg缺乏可以恢复核周围黑素小体聚集的外周黑素小体分布。然而，Mreg在黑素体运输中的功能尚不清楚。在这里，我们发现Mreg通过动力蛋白-动力蛋白运动复合物调节微管依赖的逆行黑素小体运输。Mreg与Rab-interacting lysosomal protein （RILP）的C-terminal domain相互作用，并在培养细胞中与RILP和p150(glue)（也称为dynactin亚基1，DCTN1）形成复合物，后者是dynein-dynactin运动复合物的组成部分。在正常黑素细胞中，Mreg、RILP或两者的过表达会诱导核周黑素小体聚集，而在rab27a缺陷黑素细胞中，Mreg的敲低或动力蛋白-动力蛋白运动复合物的功能破坏会恢复周围黑素小体的分布。这些发现揭示了一种新的机制，即dynein-dynactin运动复合体通过与RILP相互作用识别成熟黑素小体上的Mreg，并参与黑素小体的向心运动。
Melanoregulin (Mreg), a product of the dilute suppressor gene, has been implicated in the regulation of melanosome transport in mammalian epidermal melanocytes, given that Mreg deficiency was found to restore peripheral melanosome distribution from perinuclear melanosome aggregation in Rab27A-deficient melanocytes. However, the function of Mreg in melanosome transport has remained unclear. Here, we show that Mreg regulates microtubule-dependent retrograde melanosome transport through the dynein-dynactin motor complex. Mreg interacted with the C-terminal domain of Rab-interacting lysosomal protein (RILP) and formed a complex with RILP and p150(Glued) (also known as dynactin subunit 1, DCTN1), a component of the dynein-dynactin motor complex, in cultured cells. Overexpression of Mreg, RILP or both, in normal melanocytes induced perinuclear melanosome aggregation, whereas knockdown of Mreg or functional disruption of the dynein-dynactin motor complex restored peripheral melanosome distribution in Rab27A-deficient melanocytes. These findings reveal a new mechanism by which the dynein-dynactin motor complex recognizes Mreg on mature melanosomes through interaction with RILP and is involved in the centripetal movement of melanosomes.