Richard Mélisande, Roepman Ronald, Aartsen Wendy M, van Rossum Agnes G S H, den Hollander Anneke I, Knust Elisabeth, Wijnholds Jan, Cremers Frans P M
Institut für Genetik, Heinrich Heine Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R235-43. doi: 10.1093/hmg/ddl195.
Mutations in the Crumbs homologue 1 (CRB1) gene cause autosomal recessive retinitis pigmentosa (arRP) and autosomal Leber congenital amaurosis (arLCA). The crumbs (crb) gene was originally identified in Drosophila and encodes a large transmembrane protein required for maintenance of apico-basal cell polarity and adherens junction in embryonic epithelia. Human CRB1 and its two paralogues, CRB2 and CRB3, are highly conserved throughout the animal kingdom. Both in Drosophila and in vertebrates, the short intracellular domain of Crb/CRB organizes an evolutionary conserved protein scaffold. Several lines of evidence, obtained both in Drosophila and in mouse, show that loss-of-function of crb/CRB1 or some of its intracellular interactors lead to morphological defects and light-induced degeneration of photoreceptor cells, features comparable to those observed in patients lacking CRB1 function. In this review, we describe how understanding Crb complex function in fly and vertebrate retina enhances our knowledge of basic cell biological processes and might lead to new therapeutic approaches for patients affected with retinal dystrophies caused by mutations in the CRB1 gene.
crumbs同源物1（CRB1）基因突变会导致常染色体隐性遗传性视网膜色素变性（arRP）和常染色体遗传性莱伯先天性黑蒙（arLCA）。crumbs（crb）基因最初是在果蝇中发现的，它编码一种大型跨膜蛋白，该蛋白是胚胎上皮细胞顶-基细胞极性和黏着连接维持所必需的。人类CRB1及其两个旁系同源物CRB2和CRB3在整个动物界中高度保守。在果蝇和脊椎动物中，Crb/CRB的短细胞内结构域都能组织一个进化上保守的蛋白质支架。在果蝇和小鼠中获得的几条证据表明，crb/CRB1或其一些细胞内相互作用分子的功能丧失会导致形态缺陷和光感受器细胞的光诱导变性，这些特征与缺乏CRB1功能的患者中观察到的特征相似。在这篇综述中，我们描述了对果蝇和脊椎动物视网膜中Crb复合体功能的理解如何增进我们对基本细胞生物学过程的认识，并可能为受CRB1基因突变引起的视网膜营养不良影响的患者带来新的治疗方法。
