Biliverdin regulates NR2E3 and zebrafish retinal photoreceptor development

被引：4

作者：

Connor, Blaine ^{[1
]}

Titialii-Torres, Kayla ^{[2
]}

Rockenhaus, Abigail E. ^{[3
]}

Passamonte, Samuel ^{[3
]}

Morris, Ann C. ^{[2
]}

Lee, Young-Sam ^{[3
]}

机构：

[1] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA

[2] Univ Kentucky, Dept Biol, Lexington, KY 40506 USA

[3] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

基金：

美国国家科学基金会;

关键词：

ORPHAN NUCLEAR RECEPTOR; REV-ERB-ALPHA; HEME; GENE; TRANSCRIPTION; MUTATION; ROD; IDENTIFICATION; METABOLISM; LIGHT;

D O I：

10.1038/s41598-022-11502-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

NR2E3 is an orphan nuclear receptor whose loss-of-function causes abnormal retinal photoreceptor development and degeneration. However, despite that many nuclear receptors are regulated by binding of small molecule ligands, biological small molecule ligands regulating NR2E3 have not been identified. Identification of an endogenous NR2E3 ligand might reveal a previously unrecognized component contributing to retinal development and maintenance. Here we report that biliverdin, a conserved green pigment from heme catabolism, regulates NR2E3 and is necessary for zebrafish retinal photoreceptor development. Biliverdin from retinal extracts specifically bound to NR2E3's ligand-binding domain and induced NR2E3-dependent reporter gene expression. Inhibition of biliverdin synthesis decreased photoreceptor cell populations in zebrafish larvae, and this phenotype was alleviated by exogenously supplied biliverdin. Thus, biliverdin is an endogenous small molecule ligand for NR2E3 and a component necessary for the proper development of photoreceptor cells. This result suggests a possible role of heme metabolism in the regulation of retinal photoreceptor cell development.

引用

页数：10