A neuronal-specific mammalian homolog of the Drosophila retinal degeneration B gene with expression restricted to the retina and dentate gyrus.
Mutations in the Drosophila retinal degeneration B (rdgB) gene cause a rapid loss of the electrophysiological light response and subsequent light-enhanced photoreceptor degeneration. The rdgB gene encodes a protein with an N-terminal phosphatidylinositol transfer protein domain, a large C-terminal segment, and several hydrophobic regions thought to multiply span the subrhabdomeric cisternal membrane. A mammalian rdgB homolog (m-rdgB1) was previously identified and shown to exhibit widespread tissue distribution and functionally rescue the Drosophila rdgB mutant phenotypes. We describe a second mammalian rdgB homolog (m-rdgB2) that possesses 46% amino acid identity to Drosophila RdgB and 56% identity to M-RdgB1. M-RdgB2 possesses a neuronal-specific expression pattern, with high levels in the retina and the dentate gyrus mossy fibers and dendritic field. Using M-RdgB2-specific antibodies and subcellular fractionation, we demonstrate that M-RdgB2 is not an integral membrane protein but is stably associated with a particulate fraction through protein-protein interactions. Although transgenic expression of M-RdgB2 in rdgB2 null mutant flies suppressed the retinal degeneration, it failed to fully restore the electrophysiological light response. Because transgenic expression of M-RdgB2 does not restore the wild-type phenotype to rdgB2 mutant flies to the same extent as M-RdgB1, functional differences likely exist between the two M-RdgB homologs.
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Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D018891:Dentate Gyrus / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D005091:Exons; D005136:Eye Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D007438:Introns; D008322:Mammals; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012160:Retina / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C121270:Pitpnm2 protein, mouse; D011994:Recombinant Proteins; C068848:rdgB protein, Drosophila