Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration
Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration
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DOI：
10.1016/s0960-9822(02)01180-6
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发表时间：
2002-10-01
期刊：
影响因子：
9.2
通讯作者：
Knust, E
中科院分区：
文献类型：
--
作者：
Johnson, K;Grawe, F;Knust, E
人跨膜蛋白CRB1突变与严重形式的视网膜营养不良、视网膜色素变性12 （RP12）和Leber先天性黑内障（LCA）有关[1-3]。果蝇的同源物，面包屑，是胚胎上皮的极性和粘附所必需的[4-6]，也是粘附连接的正确形成和光感受器细胞的正确形态发生所必需的[7,8]。在这里，我们展示了果蝇碎屑的突变导致进行性、光诱导的视网膜变性。通过表达p35（一种细胞凋亡抑制剂）或通过缺乏维生素a的饮食减少视紫红质水平来防止变性。在黑暗中，横纹肌存活下来，但表现出形态发生缺陷。我们证明，这是面包屑蛋白的细胞外部分，是必不可少的，以抑制光诱导的程序性细胞死亡，而适当的形态发生取决于细胞内部分。我们得出结论，人类和果蝇的面包屑蛋白在功能上保守，以防止光依赖性光感受器变性。该实验系统现在非常适合研究RP12和lca相关视网膜变性的遗传和分子基础。
Mutations in the human transmembrane protein CRB1 are associated with severe forms of retinal dystrophy, retinitis pigmentosa 12 (RP12), and Leber's congenital amaurosis (LCA) [1-3]. The Drosophila homolog, crumbs, is required for polarity and adhesion in embryonic epithelia [4-6] and for correct formation of adherens junctions and proper morphogenesis of photoreceptor cells [7, 8]. Here, we show that mutations in Drosophila crumbs result in progressive, light-induced retinal degeneration. Degeneration is prevented by expression of p35, an inhibitor of apoptosis, or by reduction of rhodopsin levels through a vitamin A-deficient diet. In the dark, rhabdomeres survive but exhibit morphogenetic defects. We demonstrate that it is the extracellular portion of the Crumbs protein that is essential to suppress light-induced programmed cell death, while proper morphogenesis depends on the intracellular part. We conclude that human and Drosophila Crumbs proteins are functionally conserved to prevent light-dependent photoreceptor degeneration. This experimental system is now ideally suited to study the genetic and molecular basis of RP12- and LCA-related retinal degeneration.