; Zebrafish Reveals Lrp5 Can Be the Receptor of Retinol in the Visual Cycle.

Vision is essential for vertebrates including humans. Sustained vision is accomplished by retinoid metabolism, the "visual cycle," where all- retinol (atROL) is incorporated into the retinal pigment epithelium (RPE) from photoreceptors presumably through decade-long missing receptor(s). Here, we show that the LDL-related receptor-5 (Lrp5) protein is linked to the retinol binding protein 1a (Rbp1a), the transporter of atROL in the visual cycle, by generating and analyzing the digenic ; zebrafish, the same form of gene defect detected in a human case of inherited retinal degeneration. Global gene expression analysis followed by genetic study clarified that played a role downstream of . Rbp1a protein was colocalized with Lrp5 protein at microvilli of RPE cells. Furthermore, Rbp1a directly bound to the C-terminal intracellular region of Lrp5 . Collectively, these results strongly suggest that Lrp5 is a potent candidate of the receptor of atROL in the visual cycle.