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Article

A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish

1
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
2
Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia
3
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA
4
Ralph H. Johnson VA Medical Center, Division of Research, Charleston, SC 29420, USA
5
Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1099; https://doi.org/10.3390/cells9051099
Received: 17 March 2020 / Revised: 20 April 2020 / Accepted: 25 April 2020 / Published: 29 April 2020
Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is, however, not expressed in systemic tissues, where there is high affinity RBP4 binding and ROL uptake. We tested the hypothesis that the second retinol binding protein 4 receptor 2 (Rbpr2), which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR-generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, which were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatment rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival. View Full-Text
Keywords: retinol binding protein 4 receptor 2; RBP4; Rbpr2; STRA6; all-trans retinol transport; photoreceptor cell; vision; retinoids; zebrafish retinol binding protein 4 receptor 2; RBP4; Rbpr2; STRA6; all-trans retinol transport; photoreceptor cell; vision; retinoids; zebrafish
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MDPI and ACS Style

Solanki, A.K.; Kondkar, A.A.; Fogerty, J.; Su, Y.; Kim, S.-H.; Lipschutz, J.H.; Nihalani, D.; Perkins, B.D.; Lobo, G.P. A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish. Cells 2020, 9, 1099. https://doi.org/10.3390/cells9051099

AMA Style

Solanki AK, Kondkar AA, Fogerty J, Su Y, Kim S-H, Lipschutz JH, Nihalani D, Perkins BD, Lobo GP. A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish. Cells. 2020; 9(5):1099. https://doi.org/10.3390/cells9051099

Chicago/Turabian Style

Solanki, Ashish K., Altaf A. Kondkar, Joseph Fogerty, Yanhui Su, Seok-Hyung Kim, Joshua H. Lipschutz, Deepak Nihalani, Brian D. Perkins, and Glenn P. Lobo 2020. "A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish" Cells 9, no. 5: 1099. https://doi.org/10.3390/cells9051099

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