• Daniel C Berry, Hugues Jacobs, Gurdeep Marwarha, Aurore Gely-Pernot, Sheila M O'Byrne, David DeSantis, Muriel Klopfenstein, Betty Feret, Christine Dennefeld, William S Blaner, Colleen M Croniger, Manuel Mark, Noa Noy, and Norbert B Ghyselinck.
• Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
• J. Biol. Chem. 2013 Aug 23; 288 (34): 24528-39.

AbstractThe 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.

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