Lemmers Céline, Médina Emmanuelle, Lane-Guermonprez Lydie, Arsanto Jean-Pierre, Le Bivic André
UMR 6156, Laboratoire de neurogenèse et morphogenèse au cours du développement et chez l'adulte (NMDA), IBDM, Campus de Luminy, Case 907. 13288 Marseille Cedex 09. France.
Med Sci (Paris). 2004 Jun-Jul;20(6-7):663-7. doi: 10.1051/medsci/2004206-7663.
Degeneration of retina can have many causes and among the genes involved, CRB1 has been shown to be associated with Retinitis pigmentosa (RP) group 12 and Leber congenital amaurosis (LCA), two dramatic pathologies in young patients. CRB1 belongs to a family of genes conserved from Caenorhabditis elegans to human. In Drosophila melanogaster, for example, crb is essential both for the formation of the adherens junctions in epithelial cells of ectodermal origin during gastrulation and for the morphogenesis of photoreceptors in the eye. Crumbs is a transmembrane protein with a short cytoplasmic domain that interacts with scaffold proteins, Stardust and Discs lost, and with the apical cytoskeleton made of moesin and betaheavy-spectrin. The extracellular domain of Crumbs is essential for its function in photoreceptors but so far there are no known proteins interacting with it. In human, there are three known crb homologues, CRB1, 2 and 3, and CRB1 is expressed in the retina and localizes to the adherens junctions of the rods. Based on the model drawn from Drosophila, CRB1 could be involved in maintaining the morphology of rods to ensure a normal function of the retina. This is supported by the fact that the homologues of the known partners of Crumbs are also conserved in human and expressed in the retina. Understanding the precise molecular mechanism by which CRB1 acts will help to find new therapies for patients suffering from RP12 and LCA.
视网膜退化可能有多种原因，在涉及的基因中，CRB1已被证明与12型视网膜色素变性（RP）和莱伯先天性黑蒙（LCA）有关，这是两种发生在年轻患者身上的严重疾病。CRB1属于一个从秀丽隐杆线虫到人类都保守的基因家族。例如，在果蝇中，crb对于原肠胚形成期间外胚层来源上皮细胞中黏附连接的形成以及眼睛中光感受器的形态发生都至关重要。Crumbs是一种跨膜蛋白，其细胞质结构域较短，可与支架蛋白Stardust和Discs lost以及由肌动蛋白结合蛋白和β重链血影蛋白组成的顶端细胞骨架相互作用。Crumbs的细胞外结构域对于其在光感受器中的功能至关重要，但到目前为止，尚无已知的与之相互作用的蛋白质。在人类中，已知有三种crb同源物，即CRB1、2和3，其中CRB1在视网膜中表达，并定位于视杆细胞的黏附连接处。基于从果蝇得出的模型，CRB1可能参与维持视杆细胞的形态，以确保视网膜的正常功能。已知的Crumbs伙伴的同源物在人类中也保守并在视网膜中表达，这一事实支持了上述观点。了解CRB1发挥作用的确切分子机制将有助于为患有RP12和LCA的患者找到新的治疗方法。
