Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis
Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis
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DOI：
10.1038/nature721
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发表时间：
2002-03-14
期刊：
影响因子：
64.8
通讯作者：
Tepass, U
中科院分区：
文献类型：
--
作者：
Pellikka, M;Tanentzapf, G;Tepass, U
顶端跨膜蛋白Crumbs是果蝇上皮顶端-基底极性的中心调节因子。Crumbs的人类同源物CRB 1（RP 12）的功能丧失突变导致隐性视网膜营养不良，包括视网膜色素变性。在这里，我们表明，Crumbs和CRB 1本地化的感光器顶端质膜的相应子域：果蝇感光器的柄和哺乳动物感光器的内段。这些亚结构域分别支持光敏膜细胞器的形态发生和取向：杆粒和外节。果蝇碎屑是维持小带粘附完整性所必需的，在顶端膜快速扩张的过程中建立了横纹肌。面包屑还通过稳定膜相关血影蛋白细胞骨架来调节茎部发育，这一功能在机制上不同于其在上皮顶部-基底极性中的作用。我们建议，面包屑是一个核心组成部分的分子支架，控制zonula adherens大会和定义的柄作为一个顶端膜子域。这种支架的缺陷可能导致人CRB 1相关的视网膜营养不良。
The apical transmembrane protein Crumbs is a central regulator of epithelial apical-basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies.