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Structure of the STRA6 receptor for retinol uptake.

ABSTRACT: Vitamin A homeostasis is critical to normal cellular function. Retinol-binding protein (RBP) is the sole specific carrier in the bloodstream for hydrophobic retinol, the main form in which vitamin A is transported. The integral membrane receptor STRA6 mediates cellular uptake of vitamin A by recognizing RBP-retinol to trigger release and internalization of retinol. We present the structure of zebrafish STRA6 determined to 3.9-angstrom resolution by single-particle cryo-electron microscopy. STRA6 has one intramembrane and nine transmembrane helices in an intricate dimeric assembly. Unexpectedly, calmodulin is bound tightly to STRA6 in a noncanonical arrangement. Residues involved with RBP binding map to an archlike structure that covers a deep lipophilic cleft. This cleft is open to the membrane, suggesting a possible mode for internalization of retinol through direct diffusion into the lipid bilayer.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5114850 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The retinol-binding protein receptor STRA6 regulates diurnal insulin responses.

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Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor α activity.

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Retinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosis.

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The retinol-binding protein receptor STRA6 contributes to the pathogenesis of adenomyosis via Wnt/β-catenin pathway depression

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-06 | GSE242149 | GEO

The retinol-binding protein receptor STRA6 contributes to the pathogenesis of adenomyosis via Wnt/β-catenin pathway depression [RNA]

Project description:Adenomyosis is an estrogen-dependent disease in which endometrial glands and stroma are pathologically demonstrated in the myometrium. Despite its prevalence and severity of symptoms, the precise etiology and physiopathology of adenomyosis is not well understood.Vitamin defciency increase in women with adenomyosis. Much less is known about the mechanism of their relationship. We found the retinol-binding protein receptor STRA6 upregulation in uterinespiral arteries from adenomyosis patients. The increased estrogen level promote the STRA6 expression, resulting the depressed Wnt/β-catenin signaling mediated by FASN/GSK-3β interaction. Overexpression of STRA6 induced epithelial to mesenchymal transition process. miR-1249-5p achieved its negative function by regulating the target gene through 3' UTR.The depletion of STRA6 in vivo alleviated the pathogenesis of adenomyosis. These results reveal a hitherto undesribed positive feedback loop between estrogen and STRA6 in adenomyosis pathogenesis. Components of vitamin A metabolism network have more complex activities than simply controlling or transferring VA compounds between different cells.

2023-09-06 | GSE242145 | GEO

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