Dr. Hui Sun
Mechanism of a New Membrane Transport System
53-140 CHS
310- 206-4017
hsun@mednet.ucla.edu
Research Interests:
Vitamin A is essential for human survival because its derivatives (retinoids) participate in a myriad of physiological functions such as embryonic growth and development, vision, neuronal signaling, spermatogenesis, and the maintenance of immune competence and epithelium integrity. They serve as the chromophore for photoreceptor cells in vision and have profound effects on the growth and differentiation of diverse cell types by controlling the activities of their nuclear hormone receptors. Imbalance in vitamin A homeostasis can lead to a wide range of human diseases such as blindness, birth defects, neurological disorders, and susceptibility to infectious disease. Vitamin A is transported in the blood as a complex with retinol binding protein (RBP). Evidence accumulated during the past 30 years from many laboratories support the existence of a cell surface receptor for RBP that mediates vitamin A uptake. We recently identified the RBP receptor as a multitransmembrane domain protein of previously unknown function. The RBP receptor binds to RBP with high affinity and mediates cellular uptake of vitamin A from the vitamin A/RBP complex. It is widely expressed during embryonic development and in diverse organ systems such as the nervous system, the reproductive systems, the immune system, the respiratory system, and the skin–all of which are known to depend on vitamin A for proper function. The roles of the RBP receptor in development have been demonstrated in a recent human genetic study. Consistent with the diverse functions of vitamin A, mutations in the human RBP receptor gene are associated with a wide range of severe pathological phenotypes including mental retardation, anophthalmia, congenital heart defects, and lung hypoplasia. We are using several strategies to study this new membrane transport system.
Representative Publications:
Kawaguchi, R., Yu, J., Ter-Stepanian, M., Zhong, M., Guo, C., Yuan, Q., Jin, M., Travis, G.H., Ong, D., and Sun, H. Receptor-Mediated Cellular Uptake Mechanism that is Coupled to Intracellular Storage. ACS Chemical Biology (2011). Article PDF, Supplemental Materials
Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., and Sun, H. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 315:820-825 (2007) Article PDF, Supplemental Materials, Science News, Nature Research Highlight, ACS Chemical Biology Research Highlight.
Jin, M., Li, S., Moghrabi, W.N., Sun, H., and Travis, G.H. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell 122:449-459 (2005).