PUBLICATION

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

Authors
Takita, S., Seko, Y.
ID
ZDB-PUB-201201-3
Date
2020
Source
iScience   23: 101762 (Journal)
Registered Authors
Seko, Yuko, Takita, Shimpei
Keywords
Piscine Molecular Biology, Sensory Neuroscience, Transcriptomics
Datasets
GEO:GSE160663
MeSH Terms
none
PubMed
33251495 Full text @ iScience
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping