Interactions of cytoplasmic retinol-binding proteins with phospholipid vesicles: insights into the physiological functions

Vitamin A plays a key role in vision, cell growth and differentiation. In the cell, retinol has several fates: (a) it can be stored as retinyl ester of fatty acids through the action of lecithin-retinol acyl transferase (LRAT) [1]; (b) most non-esterified retinol is bound to cellular carriers (CRBP); (c) it can enter the oxidative pathway for the synthesis of retinoic acid, through the action of retinol dehydrogenases (RDH) [2]. CRBP-I is ubiquitous, whereas the homologous CRBP-II is expressed solely in the enterocytes. Our current understanding of these processes remains largely incomplete, but there is evidence that the membrane-bound LRAT and RDH are inactive towards the protein/ligand complex, suggesting that the membrane microenvironment may trigger retinol transfer from the holo protein to the enzymes. To address this hypothesis we have performed a suite of NMR experiments with CRBP-I and CRBP-II in the presence of model membranes composed of either anionic or zwitterionic phospholipids, at varying protein:lipid molar ratios and ionic strength. The results will be discussed, in comparison with our previous data collected in buffer [3, 4]. All these studies may help to understand certain aspects of the physiological functions of CRBPs. [1] J. Amengual et al. J. Biol. Chem. 287, (2012) 24216-24227. [2] S. Portè et al. Chemico-Biological Interactions 202, (2013) 186-194. [3] T. Mittag, L. Franzoni et al. J. Am. Chem. Soc. 128, (2006) 9844-9848. [4] L. Franzoni et al. J. Lipid Res. 51, (2010) 1332-1343.