Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium
Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium
复制标题
DOI：
10.1242/dev.02563
复制
发表时间：
2006-10-15
期刊：
影响因子：
4.6
通讯作者：
Wallingford, John B.
中科院分区：
文献类型：
--
作者：
Fairbank, Pamela D.;Lee, Chanjae;Wallingford, John B.
蘑菇家族蛋白质与肌动蛋白细胞骨架的控制有关，但到目前为止，只有一个家族成员在胚胎发育的背景下进行了研究。在这里，我们表明，蘑菇家族蛋白，Shroom 2（以前称为APXL）是必要的和足够的管理本地化的色素颗粒在上皮细胞的顶端表面。在缺乏Shroom 2功能的非洲爪蟾胚胎中，我们观察到眼睛色素沉着的缺陷，这是由于黑素体未能成熟并与顶端细胞表面相关联。Shroom 2在幼稚上皮细胞中的异位表达促进顶端色素积累，并且这种活性特别需要Rab 27 a GT3。最有趣的是，我们发现Shroom 2，像Shroom 3（以前称为Shroom），足以诱导微管成核蛋白γ-微管蛋白在幼稚上皮细胞顶端表面的急剧顶端积累。总之，我们的数据将Shroom 2确定为RPE色素沉着的中央调节器，并表明尽管它们具有不同的生物学作用，但Shroom家族蛋白具有共同的活性。最后，由于编码人SHROOM 2的基因座位于两种不同形式的眼白化病的关键区域内，因此SHROOM 2突变可能是这些人类视觉系统疾病的促成因素。
Shroom family proteins have been implicated in the control of the actin cytoskeleton, but so far only a single family member has been studied in the context of developing embryos. Here, we show that the Shroom-family protein, Shroom2 (previously known as APXL) is both necessary and sufficient to govern the localization of pigment granules at the apical surface of epithelial cells. In Xenopus embryos that lack Shroom2 function, we observed defects in pigmentation of the eye that stem from failure of melanosomes to mature and to associate with the apical cell surface. Ectopic expression of Shroom2 in naive epithelial cells facilitates apical pigment accumulation, and this activity specifically requires the Rab27a GTPase. Most interestingly, we find that Shroom2, like Shroom3 (previously called Shroom), is sufficient to induce a dramatic apical accumulation of the microtubule-nucleating protein gamma-tubulin at the apical surfaces of naive epithelial cells. Together, our data identify Shroom2 as a central regulator of RPE pigmentation, and suggest that, despite their diverse biological roles, Shroom family proteins share a common activity. Finally, because the locus encoding human SHROOM2 lies within the critical region for two distinct forms of ocular albinism, it is possible that SHROOM2 mutations may be a contributing factor in these human visual system disorders.