Regulation of melanosome number, shape and movement in the zebrafish retinal pigment epithelium by OA1 and PMEL.
Regulation of melanosome number, shape and movement in the zebrafish retinal pigment epithelium by OA1 and PMEL.
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DOI：
10.1242/jcs.164400
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发表时间：
2015-04-01
影响因子：
4
通讯作者：
Futter CE
中科院分区：
文献类型：
--
作者：
Burgoyne T;O'Connor MN;Seabra MC;Cutler DF;Futter CE
视网膜色素上皮（RPE）中黑素体生物发生的分析是具有挑战性的，因为它主要发生在短的胚胎时间窗口。在这里，我们表明，斑马鱼提供了一个理想的模型系统，研究这一过程，因为在RPE的黑素体生物合成的时间有利于分子操纵使用morpholinos。吗啉代介导的OA1（也称为GPR143）敲除，其在人类同源物中的突变引起最常见形式的人类眼白化病，诱导黑素体数量的大幅减少，重现了哺乳动物疾病的关键特征，其中黑素体数量减少先于大黑素体形成。我们进一步表明，PMEL，哺乳动物黑素体生物发生的关键组成部分，是需要在斑马鱼的圆柱形黑素体的产生，这反过来又是需要黑素体运动到顶端的过程和维持感光细胞的完整性。含有相似黑色素体积的球形和圆柱形黑色素体共存于细胞体中，但只有圆柱形黑色素体进入顶突。两者合计，我们的研究结果表明，黑素体的数量和形状是独立的调节和黑素体的形状控制的功能，在视网膜色素上皮，取决于本地化的顶端过程。
Analysis of melanosome biogenesis in the retinal pigment epithelium (RPE) is challenging because it occurs predominantly in a short embryonic time window. Here, we show that the zebrafish provides an ideal model system for studying this process because in the RPE the timing of melanosome biogenesis facilitates molecular manipulation using morpholinos. Morpholino-mediated knockdown of OA1 (also known as GPR143), mutations in the human homologue of which cause the most common form of human ocular albinism, induces a major reduction in melanosome number, recapitulating a key feature of the mammalian disease where reduced melanosome numbers precede macromelanosome formation. We further show that PMEL, a key component of mammalian melanosome biogenesis, is required for the generation of cylindrical melanosomes in zebrafish, which in turn is required for melanosome movement into the apical processes and maintenance of photoreceptor integrity. Spherical and cylindrical melanosomes containing similar melanin volumes co-exist in the cell body but only cylindrical melanosomes enter the apical processes. Taken together, our findings indicate that melanosome number and shape are independently regulated and that melanosome shape controls a function in the RPE that depends on localisation in the apical processes.
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影响因子：
3.5
作者：
d'Addio, M;Pizzigoni, A;Schiaffino, MV
通讯作者：
Schiaffino, MV
影响因子：
4.5
作者：
Hellström AR;Watt B;Fard SS;Tenza D;Mannström P;Narfström K;Ekesten B;Ito S;Wakamatsu K;Larsson J;Ulfendahl M;Kullander K;Raposo G;Kerje S;Hallböök F;Marks MS;Andersson L
通讯作者：
Andersson L
影响因子：
6.5
作者：
JIMBOW, K;OIKAWA, O;TAKEUCHI, T
通讯作者：
TAKEUCHI, T
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
--
作者：
Barsoum, I. B.;King-Smith, C.
通讯作者：
King-Smith, C.