Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 17 March 2020 / Approved: 19 March 2020 / Online: 19 March 2020 (03:16:19 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Cells 2020, 9, 1099
DOI: 10.3390/cells9051099

Abstract

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, that were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatments 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.

Subject Areas

retinol binding protein 4 receptor 2; RBP4; Rbpr2; STRA6; all-trans retinol transport; photoreceptor cell; vision; retinoids; zebrafish

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