title: The STRA6 receptor is essential for retinol-binding protein-induced insulin resistance but not for maintaining vitamin A homeostasis in tissues other than the eye.
abstract: The plasma membrane protein STRA6 is thought to mediate uptake of retinol from its blood carrier retinol-binding protein (RBP) into cells and to function as a surface receptor that, upon binding of holo-RBP, activates a JAK/STAT cascade. It was suggested that STRA6 signaling underlies insulin resistance induced by elevated serum levels of RBP in obese animals. To investigate these activities in vivo, we generated and analyzed Stra6-null mice. We show that the contribution of STRA6 to retinol uptake by tissues in vivo is small and that, with the exception of the eye, ablation of Stra6 has only a modest effect on retinoid homeostasis and does not impair physiological functions that critically depend on retinoic acid in the embryo or in the adult. However, ablation of Stra6 effectively protects mice from RBP-induced suppression of insulin signaling. Thus one biological function of STRA6 in tissues other than the eye appears to be the coupling of circulating holo-RBP levels to cell signaling, in turn regulating key processes such as insulin response.
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Berry
authors.forename: Hugues
authors.initials: H
authors.lastname: Jacobs
authors.forename: Gurdeep
authors.initials: G
authors.lastname: Marwarha
authors.forename: Aurore
authors.initials: A
authors.lastname: Gely-Pernot
authors.forename: Sheila M
authors.initials: SM
authors.lastname: O'Byrne
authors.forename: David
authors.initials: D
authors.lastname: DeSantis
authors.forename: Muriel
authors.initials: M
authors.lastname: Klopfenstein
authors.forename: Betty
authors.initials: B
authors.lastname: Feret
authors.forename: Christine
authors.initials: C
authors.lastname: Dennefeld
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Croniger
authors.forename: Manuel
authors.initials: M
authors.lastname: Mark
authors.forename: Noa
authors.initials: N
authors.lastname: Noy
authors.forename: Norbert B
authors.initials: NB
authors.lastname: Ghyselinck
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D005123:Eye; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D007328:Insulin; D008565:Membrane Proteins; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma; C108001:Stra6 protein, mouse; D014801:Vitamin A
keywords: Adipokines; Insulin Resistance; Jak Kinase; Obesity; Phospholipid; RBP4; STAT Transcription Factor; Vitamin A