title: Liver retinol transporter and receptor for serum retinol-binding protein (RBP4).
abstract: 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.
authors.affiliation: Molecular Medicine Program and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Philomena
authors.initials: P
authors.lastname: Alapatt
authors.forename: Fangjian
authors.initials: F
authors.lastname: Guo
authors.forename: Susan M
authors.initials: SM
authors.lastname: Komanetsky
authors.forename: Shuping
authors.initials: S
authors.lastname: Wang
authors.forename: Jinjin
authors.initials: J
authors.lastname: Cai
authors.forename: Ashot
authors.initials: A
authors.lastname: Sargsyan
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rodríguez Díaz
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Bacon
authors.forename: Pratik
authors.initials: P
authors.lastname: Aryal
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Graham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D008565:Membrane Proteins; C101326:RBP4 protein, human; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma; C108001:Stra6 protein, mouse