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- Yong Yu
ProfessorGraduate Director
Molecular and Cellular Physiology and Neurobiology.
Research Overview
Ion channels and ion-channel-coupled receptors are cell membrane proteins that sense physical and chemical signals and couple them with ionic flux through the cell membrane. Ion channel activity is essential for the function of almost all organs and organ systems, including the heart, the lung, the kidney, the muscular system, the nervous system, and the immune system. Consequently, the malfunction of ion channels is related to many human diseases, and ion channels have served as major drug targets.
The research in Yu lab is focusing on the molecular mechanisms of assembly, function and regulation of ion channels and membrane receptors. Currently we are interested in the transient receptor potential (TRP) channels, proteins which are essential for sensory physiology and have been shown to play crucial roles in human diseases. So far, TRP channels has been shown to be involved in the formation of sight, hearing, touch, smell, taste, temperature, and pain sensation. We use cultured mammalian cells, Xenopus oocytes and zebrafish as model systems, and study structure and function of ion channels and receptors with a combined molecular biology, biochemistry, biophysics, x-ray crystallography, and electrophysiology approach.
Research in Yu lab is funded by the National Institutes of Health and the PKD Foundation.
1. Zhifei Wang, Mengying Chen, Qiang Su, Tiago D. C. Morais, Yan Wang, Elianna Nazginov, Akhilraj R. Pillai, Feng Qian, Yigong Shi, Yong Yu, Molecular and structural basis of the dual regulation of the polycystin-2 ion channel by small-molecule ligands, Proc. Natl. Acad. Sci. USA (PNAS), 121 (12) e2316230121, https://doi.org/10.1073/pnas.2316230121, 2024
2. Shuai Gao; Xia Yao; Jiaofeng Chen, Gaoxingyu Huang, Xiao Fan, Lingfeng Xue, Zhangqiang Li, Tong Wu, Yupeng Zheng, Jian Huang, Xueqin Jin, Yan Wang, Zhifei Wang, Yong Yu, Lei Liu, Xiaojing Pan, Chen Song, and Nieng Yan, Structural basis for human Cav1.2 inhibition by multiple drugs and the neurotoxin calciseptine, Cell, 186, 5363–5374, https://doi.org/10.1016/j.cell.2023.10.007, 2023
3. Yan Wang, Zhifei Wang, Mahmud Arif Pavel, Courtney Ng, Parul Kashyap, Bin Li, Gabriella A. Ulloa, and Yong Yu, The diverse effects of pathogenic point mutations on ion channel activity of a gain-of-function polycystin-2. J Biol Chem, 299(5), 104674, https://doi.org/10.1016/j.jbc.2023.104674. 2023.
4. Xia Yao, Yan Wang, Zhifei Wang, Xiao Fan, Di Wu, Jian Huang, Alexander Mueller, Sarah Gao, Miaohui Hu, Carol V. Robinson, Yong Yu, Shuai Gao, and Nieng Yan, Structure of R-type human Cav2.3 channel reveal conformational crosstalk of the intracellular segments. Nature Communications, 13, 7358 https://doi.org/10.1038/s41467-022-35026-6, 2022
5. Xia Yao, Shuai Gao, Jinxin Wang, Zhangqiang Li, Jian Huang, Yan Wang, Zhifei Wang, Jiaofeng Chen, Xiao Fan, Weipengg Wang, Xueqin Jin, Xiaojing Pan, Yong Yu, Armando Lagrutta, and Nieng Yan, Structural basis for the severe adverse interaction of sofosbuvir and amiodarone on L-type Cav channels. Cell, 185(25), 4801-4810, doi:10.1016/j.cell.2022.10.024, 2022
6. Bin Li, Yan Wang, Alexis Castro, Courtney Ng, Zhifei Wang, Haroon Chaudhry, Zainab Agbaje, Gabriella A. Ulloa, and Yong Yu, The roles of two extracellular loops in proton sensing and permeation in human Otop1 channel. Communications Biology, 5, 1110. https://doi.org/10.1038/s42003-022-04085-2, 2022
7. Herui Wang, Bing Li, Kulsum Asha, Ryan L. Pangilinan, Asha Thuraisamy, Harman Chopra, Susumu Rokudai, Yong Yu, Carol L. Prives, and Yan Zhu, The ion channel TRPM7 regulates zinc depletion-induced MDMX degradation. J Biol Chem, 297(5) 101292. doi: 10.1016/j.jbc.2021.101292, 2021
8. Qiang Su*, Mengying Chen, Yan Wang, Bin Li, Dan Jing, Xiechao Zhan, Yong Yu*, and Yinggong Shi*, Structural basis for Ca2+ activation of the heteromeric PKD1L3/PKD2L1 channel. Nature Communications 12, 4871, https://doi.org/10.1038/s41467-021-25216-z, 2021, *corresponding authors
9. Zhifei Wang, Courtney Ng, Xiong Liu, Yan Wang, Bin Li, Parul Kashyap, Haroon A. Chaudhry, Alexis Castro, Enessa M. Kalontar, Leah Ilyayev, Rebecca Walker, R. Todd Alexander, Feng Qian, Xing-Zhen Chen, and Yong Yu, The ion channel function of polycystin-1 in the polycystin-1/polycystin-2 complex, EMBO Reports, 20: e48336, doi:10.15252/embr.201948336, 2019
Commentary “Holding open the door reveals a new view of polycystin channel function” by Dr. Michael Caplan, EMBO Reports, 20: e49156, doi.org/10.15252/embr.201949156, 2019.
10. Parul Kashyap, Courtney Ng, Zhifei Wang, Bin Li, Hannah Martin, and Yong Yu, A PKD1L3 splice variant in taste buds is not cleaved at the G protein-coupled receptor proteolytic site, Biochem. Biophys. Res. Commun., 512 (4): 812-818, 2019.
11. Courtney Ng, Zhifei Wang, Bin Li, and Yong Yu, Electrophysiological recording of a gain-of-function polycystin-2 channel with two-electrode voltage clamp. Polycystic Kidney Disease (Hu, J. and Yu, Y. ed.), Boca Raton (FL): CRC Press/Taylor & Francis, 2019, P68-86.
12. Wang Zheng, Xiaoyong Yang, Ruikun Hu, Ruiqi Cai, Laura Hofmann, Zhifei Wang, Qiaolin Hu, Xiong Liu, David Bulkey, Yong Yu, Jingfeng Tang, Veit Flockerzi, Ying Cao, Erhu Cao, and Xing-Zhen Chen, Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels. Nature communications 9, 2302, doi:10.1038/s41467-018-04586-x, 2018.
13. Thomas L. Lamson, Sahar Khan, Zhifei Wang, Yun-Kai Zhang, Yong Yu, Zhe-Sheng Chen, and Huizhong Xu, Patterned Synthesis of ZnO Nanorod Arrays for Nanoplasmonic Waveguide Applications. Optics Communications, 411: 53–58, 2018
14. Zahra Salehi-Najafabadi, Bin Li, Victoria Valentino, Courtney Ng, Hannah Martin, Yang Yu, Zhifei Wang, Parul Kashyap, and Yong Yu, Extracellular loops are essential for the assembly and function of polycystin receptor-ion channel complexes. J Biol Chem, 292, 4210-4221, 2017.
15. Mahmud Arif Pavel, Caixia Lv, Courtney Ng, Lei Yang, Parul Kashyap, Clarissa Lam, Victoria Valentino, Helen Fung, Thomas Campbell, Simon G. Møller, David Zenisek, Nathalia G. Holtzman, and Yong Yu, Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant. Proc. Natl. Acad. Sci. USA(PNAS), 113 (17) E2363-E2372, 2016
16. Michailidis I.E., Abele K., Zhang W.K., Lin B., Yu Y., Geyman L., Ehlers M.D., Pnevmatikakis E.A., and Yang J., Age-related homeostatic mid-channel proteolysis of L-type voltage-gated Ca2+ channels. Neuron, 82(5):1045-57, 2014.
17. Chen, G., Lu J., Lam C., and Yu Y., A novel green synthesis approach for polymernanocomposites decorated with silvernanoparticles and their antibacterial activity, Analyst, 139, 5794-5800, 2014.
18. Zhang K., Novak O., Wei Z., Gou M., Zhang X., Yu Y., Yang H., Cai Y., Strnad M., and Liu C.-J. Arabidopsis ABCG14 protein controls the acropetal translocation of root-synthesized cytokinins. Nature Communications, 5:3274 doi:10.1038/ncomms4272, 2014.
19. Lam C., Arif Pavel M., Kashyap P., Salehi-Najafabadi Z., Valentino V., and Yu Y., Detection of CXCR2 Cytokine Receptor Surface Expression Using Immunofluorescence. Methods in Molecular Biology, 1172:193-200, 2014.
20. Arif Pavel M., Lam C., Kashyap P., Salehi-Najafabadi Z., Singh G., and Yu Y., Analysis of the Cell Surface Expression of Cytokine Receptors Using the Surface Protein Biotinylation Method. Methods in Molecular Biology, 1172:185-192, 2014.
21. Yu Y., Ulbrich M.H., Dobbins S., Li M.-H., Zhang K. W., Isacoff E.Y., and Yang J., Molecular mechanism of the assembly of an acid-sensing receptor/ion channel complex. Nature Communications. 3:1252 doi: 10.1038/ncomms2257, 2012
22. Zhu J*., Yu Y*, Ulbrich M. H., Li M.-H., Isacoff E. Y., Honig B., and Yang J., Structural model of the TRPP2/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach. Proc. Natl. Acad. Sci. USA (PNAS), 108(25):10133-10138, 2011. (*equal contribution)
23. Li M.-H., Yu Y., and Yang J., Structural biology of TRP channels. (In: Md. Shahidul Islam (Ed.). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology 704: 1-23, 2011.
24. Yu Y., Ulbrich M.H., Li M.-H., Buraei Z., Chen X.-Z., Ong A.C. M., Tong L., Isacoff E.Y., and Yang J., Structural model of the TRPP2/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach. Proc. Natl. Acad. Sci. USA (PNAS), 106(28):11558-63, 2009.