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The Journal of Neuroscience, September 1, 1999, 19(17):7317-7325

A Neuronal-specific Mammalian Homolog of the Drosophila Retinal Degeneration B Gene with Expression Restricted to the Retina and Dentate Gyrus

Changwan Lu¹, Thomas S. Vihtelic², David R. Hyde², and Tiansen Li¹

¹ Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, and ² Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556

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.

Key words: rdgB; retinal degeneration; PITP; dentate gyrus; hippocampus; autism

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19177317-09$05.00/0

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