ArticleMolecular and cellular biology2012
Transthyretin blocks retinol uptake and cell signaling by the holo-retinol-binding protein receptor STRA6.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 70 citations in OpenAlex.
- Beyond a gatekeeper: the non-classical signaling role of STRA6 in driving endothelial senescence and atherosclerosis.Frontiers in immunology · 2026Review
- Body mass index modifies the association between transthyretin concentrations and gestational diabetes mellitus across pregnancy trimesters.BMC pregnancy and childbirth · 2025Article
- Retinol binding protein 4 enhances cellular cholesterol uptake to facilitate influenza A virus infection.PLoS pathogens · 2025Article
- Associations of maternal serum transthyretin concentration with pregnancy and birth outcomes.BMC pregnancy and childbirth · 2025Article
- Retinol binding protein 4 and type 2 diabetes: from insulin resistance to pancreatic β-cell function.Endocrine · 2024Review
- Article
- The Role and Mechanism of Retinol and Its Transformation Product, Retinoic Acid, in Modulating Oxidative Stress-Induced Damage to the Duck Intestinal Epithelial Barrier In Vitro.Animals : an open access journal from MDPI · 2023Article
- Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease.Nutrients · 2022Review
- The Role of Vitamin A in Retinal Diseases.International journal of molecular sciences · 2022Review
- AllCurrent research in immunology · 2022Review
- STRA6 and Placental Retinoid Metabolism in Gestational Diabetes Mellitus.Journal of personalized medicine · 2021Article
- Obesity alters the ovarian proteomic response to zearalenone exposure†.Biology of reproduction · 2021Article
- Biological Functions of RBP4 and Its Relevance for Human Diseases.Frontiers in physiology · 2021Review
- Association between transthyretin concentrations and gestational diabetes mellitus in Chinese women.Archives of gynecology and obstetrics · 2020Article
- DNA methylation changes in infants between 6 and 52 weeks.Scientific reports · 2019Article
- Genetic architecture of retinoic-acid signaling-associated ocular developmental defects.Human genetics · 2019Review
- Radiation-induced overexpression of transthyretin inhibits retinol-mediated hippocampal neurogenesis.Scientific reports · 2018Article
- Adipokine RBP4 drives ovarian cancer cell migration.Journal of ovarian research · 2018Article
- Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases.Mediators of inflammation · 2018Review
- The Retinol Circulating Complex Releases Hormonal Ligands During Acute Stress Disorders.Frontiers in endocrinology · 2018Review
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4 authors at 2 institutions in 2 countries.
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Abstract
Vitamin A is secreted from cellular stores and circulates in blood bound to retinol-binding protein (RBP). In turn, holo-RBP associates in plasma with transthyretin (TTR) to form a ternary RBP-retinol-TTR complex. It is believed that binding to TTR prevents the loss of RBP by filtration in the kidney. At target cells, holo-RBP is recognized by STRA6, a plasma membrane protein that serves a dual role: it mediates uptake of retinol from extracellular RBP into cells, and it functions as a cytokine receptor that, upon binding holo-RBP, triggers a JAK/STAT signaling cascade. We previously showed that STRA6-mediated signaling underlies the ability of RBP to induce insulin resistance. However, the role that TTR, the binding partner of holo-RBP in blood, plays in STRA6-mediated activities remained unknown. Here we show that TTR blocks the ability of holo-RBP to associate with STRA6 and thereby effectively suppresses both STRA6-mediated retinol uptake and STRA6-initiated cell signaling. Consequently, TTR protects mice from RBP-induced insulin resistance, reflected by reduced phosphorylation of insulin receptor and glucose tolerance tests. The data indicate that STRA6 functions only under circumstances where the plasma RBP level exceeds that of TTR and demonstrate that, in addition to preventing the loss of RBP, TTR plays a central role in regulating holo-RBP/STRA6 signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.