Liver Retinol Transporter and Receptor for Serum Retinol-binding Protein (RBP4)

Vitamin A (retinol) is absorbed in the small intestine, stored in liver, and secreted into circulation bound to serum retinol-binding protein (RBP4). Circulating retinol may be taken up by extrahepatic tissues or recycled back to liver multiple times before it is finally metabolized or degraded. Liv...

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Bibliographic Details
Published in:The Journal of biological chemistry 2013-01, Vol.288 (2), p.1250-1265
Main Authors: Alapatt, Philomena, Guo, Fangjian, Komanetsky, Susan M., Wang, Shuping, Cai, Jinjin, Sargsyan, Ashot, Rodríguez Díaz, Eduardo, Bacon, Brandon T., Aryal, Pratik, Graham, Timothy E.
Format: Article
Language:English
Subjects:
Adipokines
Amino Acid Sequence
Animals
Base Sequence
Carrier Proteins - metabolism
Cell Line
Cloning, Molecular
Diabetes
DNA Primers
Humans
Insulin Resistance
Liver - metabolism
Membrane Proteins - genetics
Metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Obesity
Polymerase Chain Reaction
Promoter Regions, Genetic
RBP4, Retinol-binding Protein
Receptors
Retinoid-binding Protein
Retinol-Binding Proteins, Plasma - metabolism
Sequence Homology, Amino Acid
Stra6
Transcriptome
Vitamin A
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Summary:Vitamin A (retinol) is absorbed in the small intestine, stored in liver, and secreted into circulation bound to serum retinol-binding protein (RBP4). Circulating retinol may be taken up by extrahepatic tissues or recycled back to liver multiple times before it is finally metabolized or degraded. Liver exhibits high affinity binding sites for RBP4, but specific receptors have not been identified. The only known high affinity receptor for RBP4, Stra6, is not expressed in the liver. Here we report discovery of RBP4 receptor-2 (RBPR2), a novel retinol transporter expressed primarily in liver and intestine and induced in adipose tissue of obese mice. RBPR2 is structurally related to Stra6 and highly conserved in vertebrates, including humans. Expression of RBPR2 in cultured cells confers high affinity RBP4 binding and retinol transport, and RBPR2 knockdown reduces RBP4 binding/retinol transport. RBPR2 expression is suppressed by retinol and retinoic acid and correlates inversely with liver retinol stores in vivo. We conclude that RBPR2 is a novel retinol transporter that potentially regulates retinol homeostasis in liver and other tissues. In addition, expression of RBPR2 in liver and fat suggests a possible role in mediating established metabolic actions of RBP4 in those tissues. Background: Mechanisms by which RBP4 interacts with cells are not completely understood. Results: 1300002K09Rik (RBPR2) is identified as a Stra6-related protein expressed in liver, intestine, and obese fat that mediates RBP4 binding and retinol transport. Conclusion: RBPR2 is a novel RBP4 receptor that mediates retinol uptake. Significance: RBPR2 may be important for whole body retinol homeostasis or cellular actions of RBP4 in certain tissues.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M112.369132