In the bloodstream, circulating retinol binding protein 4 (RBP4, in complex with atROL), binds transthyretin (TTR, a 51 kDa protein) in a 1:1 molar complex (Naylor & Newcomer, 1999). The resultant TTR:RBP4:atROL complex is larger and therefore less susceptible to glomerular filtration, maintaining normal levels of retinoid and RBP4 in the circulation. In TTR-deficient mice, plasma levels of atROL and RBP4 were observed to be 5% of wild type levels, highlighting the importance of TTR binding to RBP4:atROL (Episkopou et al. 1993). TTR is also a transporter for thyroxine in the brain (not shown here) (Herbert et al. 1986).
All-trans-retinol (atROL) circulates in the bloodstream in complex with transthyretin (TTR) and retinol- binding protein 4 (RBP4). The receptor Stimulated by retinoic acid gene 6 protein homologue (STRA6) acts as a high-affinity cell-surface receptor for the complex (Berry et al. 2012), removing atROL and transporting it into tissues expressing STRA6, including the eyes (Kawaguchi et al. 2007).