title: Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration.
abstract: 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). The Drosophila homolog, crumbs, is required for polarity and adhesion in embryonic epithelia and for correct formation of adherens junctions and proper morphogenesis of photoreceptor cells. 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.
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D017344:Genes, Insect / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008027:Light; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014802:Vitamin A Deficiency
chemical_list: D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D014764:Viral Proteins; C064360:crb protein, Drosophila; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus