eys +/- ; lrp5 +/- Zebrafish Reveals Lrp5 Can Be the Receptor of Retinol in the Visual Cycle

Shimpei Takita; Yuko Seko

doi:10.1016/j.isci.2020.101762

eys ^+/- ; lrp5 ^+/- Zebrafish Reveals Lrp5 Can Be the Receptor of Retinol in the Visual Cycle

iScience. 2020 Nov 3;23(12):101762. doi: 10.1016/j.isci.2020.101762. eCollection 2020 Dec 18.

Authors

Shimpei Takita¹, Yuko Seko¹

Affiliation

¹ Visual Functions Section, Department of Rehabilitation for Sensory Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan.

Abstract

Vision is essential for vertebrates including humans. Sustained vision is accomplished by retinoid metabolism, the "visual cycle," where all-trans 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 eyes shut homolog ^+/- ; lrp5 ^+/- 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 rbp1a played a role downstream of lrp5. Rbp1a protein was colocalized with Lrp5 protein at microvilli of RPE cells. Furthermore, Rbp1a directly bound to the C-terminal intracellular region of Lrp5 in vitro. Collectively, these results strongly suggest that Lrp5 is a potent candidate of the receptor of atROL in the visual cycle.

Keywords: Piscine Molecular Biology; Sensory Neuroscience; Transcriptomics.