Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6

Vitamin A has biological functions as diverse as sensing light for vision, regulating stem cell differentiation, maintaining epithelial integrity, promoting immune competency, regulating learning and memory, and acting as a key developmental morphogen. Vitamin A derivatives have also been used in treating human diseases. If vitamin A is considered a drug that everyone needs to take to survive, evolution has come up with a natural drug delivery system that combines sustained release with precise and controlled delivery to the cells or tissues that depend on it. This "drug delivery system" is mediated by plasma retinol binding protein (RBP), the principle and specific vitamin A carrier protein in the blood, and STRA6, the cell-surface receptor for RBP that mediates cellular vitamin A uptake. The mechanism by which the RBP receptor absorbs vitamin A from the blood is distinct from other known cellular uptake mechanisms. This review summarizes recent progress in elucidating the fundamental molecular mechanism mediated by the RBP receptor and multiple newly discovered catalytic activities of this receptor, and compares this transport system with retinoid transport independent of RBP/STRA6. How to target this new type of transmembrane receptor using small molecules in treating diseases is also discussed.