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Hui Sun, PhD
Membrane Receptors and Transporters: Mechanisms and Roles in Human Diseases
53-140 CHS
310- 206-4017

Research Interests:

Light is a rich information source. From the human perspective, light is defined as the region of the electromagnetic spectrum that we can see. For billions of years, diverse organisms selected vitamin A-based light sensors for vision or the equivalent of vision, although there exist other choices of light sensors. Vitamin A-based light sensors in unicellular organisms are light-gated ion channels, while those in multicellular organisms are light-activated G-protein coupled receptors (Figure 1). Vitamin A-based light sensors span a wide range of absorption maxima from UV to near infrared. This range matches the peak irradiance of sunlight, the dominant light source throughout evolution.

Although for most of evolutionary history, vitamin A has been used as a light sensor, its biological functions tremendously expanded about half a billion years ago. In addition to its essential roles in vision, vitamin A derivatives (retinoids) have diverse biological functions including its roles in embryonic development, neuronal signaling, and the maintenance of immune competence and epithelial integrity. However, due to its potent biological activities, excessive retinoid is toxic. How is it possible to transport vitamin A to the right place, at the right time and at the right dosage? The principle and specific vitamin A carrier in the blood is plasma retinol binding protein (RBP). It was hypothesized in the 1970s that there exists a membrane receptor for RBP that acts as a "loading dock" to unload vitamin A. The identity of the RBP receptor was revealed a few years ago as a multitransmembrane domain protein that represents a new type of cell-surface receptor. This membrane 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 eye, 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. Mutations in the human RBP receptor gene are associated with a wide range of pathological phenotypes including anophthalmia, mental retardation, congenital heart defects, and lung hypoplasia. We are developing innovative strategies to study this new membrane transport system (Figure 2).

Representative Publications:

Cheng, G., Zhong, M., Kawaguchi, R., Kassai, M., Al-Ubaidi, M., Deng, J., Ter-Stepanian, M., and Sun, H. (2014) Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF. eLife 4 (doi: 10.7554/eLife.05401). Article PDF

Kawaguchi, R., Yu, J., Ter-Stepanian, M., Zhong, M., Guo, C., Yuan, Q., Jin, M., Travis, G.H., Ong, D., and Sun, H. (2011) Receptor-Mediated Cellular Uptake Mechanism that is Coupled to Intracellular Storage. ACS Chemical Biology 6:1041-51 . Article PDF, Supplemental Materials

Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., and Sun, H. (2007) A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 315:820-825 Article PDF, Supplemental Materials, Science News, Nature Research Highlight, ACS Chemical Biology Research Highlight. Faculty of 1000

Complete publication list