Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
J Cell Sci. 2012 Mar 15;125(Pt 6):1508-18. doi: 10.1242/jcs.094185. Epub 2012 Jan 24.
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.
黑素皮质素（Mreg）是稀释抑制基因的产物，已被认为参与调节哺乳动物表皮黑素细胞中的黑素小体运输，因为发现 Mreg 缺乏可恢复 Rab27A 缺陷黑素细胞中核周黑素小体聚集的外围黑素小体分布。然而，Mreg 在黑素小体运输中的功能仍不清楚。在这里，我们表明 Mreg 通过动力蛋白 - 动力蛋白复合物调节微管依赖性逆行黑素小体运输。Mreg 与 Rab 相互作用的溶酶体蛋白（RILP）的 C 末端结构域相互作用，并与 RILP 和 p150(Glued)（也称为动力蛋白 dynactin 复合物亚基 1，DCTN1）形成复合物，后者是动力蛋白 dynactin 复合物的一个组成部分，在培养的细胞中。正常黑素细胞中 Mreg、RILP 或两者的过表达诱导核周黑素小体聚集，而 Mreg 的敲低或动力蛋白 dynactin 复合物的功能破坏则恢复了 Rab27A 缺陷黑素细胞中外围黑素小体的分布。这些发现揭示了一种新的机制，即通过与 RILP 的相互作用，动力蛋白 dynactin 复合物识别成熟黑素小体上的 Mreg，并参与黑素小体的向心性运动。
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