Retinoic Acid Receptors and Cellular Retinoid Binding Proteins: Complex Interplay in Retinoid Signaling*

VITAMIN A and its biologically active derivatives, retinal and retinoic acid (RA), are essential for the health and survival of the individual. These natural compounds, together with a large repertoire of synthetic analogs, are collectively referred to as retinoids. In addition to their well known role in vision, retinoids are required for reproduction, act as morphogenetic agents during embryonic development, and regulate the growth and differentiation of a wide variety of cell types throughout the life of the organism. Although the role of 11-cis-retinal as the chromophore component of the photoreceptors in the visual cycle was elucidated three decades ago (1), the general mechanism by which RA influences cellular activities has been unraveled only relatively recently. In fact, our present understanding of how retinoids control cell functions stems directly from studies of steroid and thyroid hormones' action. These pioneering studies demonstrated that small hydrophobic ligands are able to cross passively biological membranes and control cell functions by using specific intracellular receptors as signal transducers.