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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.

Rôle des protéines Crumbs dans le contrôle de la morphogenèse des cellules épithéliales et des photorécepteurs