Cloning and tissue localization of a novel zebrafish RdgB homolog that lacks a phospholipid transfer domain.

The retinal degeneration B (RdgB) protein family is characterized by an amino-terminal phosphatidylinositol transfer protein (PITP) domain, several hydrophobic domains, and a highly conserved carboxyl terminus. We identified a zebrafish RdgB homolog (pl-RdgB) that lacks the amino-terminal PITP domain, while retaining over 45% amino acid identity with the two mouse RdgB proteins (M-RdgB1 and M-RdgB2). Unlike the widespread retinal expression observed for other vertebrate RdgB homologs, pl-RdgB is restricted in the retina to the cone cell inner segments. The pl-RdgB protein is also expressed in the brain, although its distribution is different than the other RdgB homologs. Analogous to M-RdgB2, pl-RdgB protein is extracted from a retinal homogenate by guanidine and not by Triton X-100. Thus, pl-RdgB and likely all the identified RdgB homologs are not integral membrane proteins, but may associate with the membrane through protein-protein interactions. While expression of either murine RdgB homolog restored the defective light response and prevented retinal degeneration in rdgB mutant flies, expressing zebrafish pl-RdgB in Drosophila rdgB2 null mutants slowed retinal degeneration without restoring the electrophysiological light response. Thus, pl-RdgB may define a previously unrecognized protein family, which includes the other RdgB homologs, that act through a protein complex to maintain photoreceptor viability.