Molecular Neurophysiology Laboratory Xian-Min Yu, D.Sc.H. Florida State University College of Medicine Dept. of Biomedical Sciences 1115 West Call Street Tallahassee, FL 32306-4300 MSR 2300-C Office: (850) 645-2718 Dr. Yu's Faculty Profile RESEARCH POSITIONS OPEN FOR POSTDOCTORAL, GRADUATE AND UNDERGRADUATE STUDENTS
Research Interests
Research in this lab is primarily focused on mechanisms underlying functional plasticity of neurons associated with pathophysiological processes in the central nervous system, such as neuronal degeneration, chronic pain and mental disorders. Since glutamate, particularly N-methyl-D-arspartate (NMDA) subtype, receptors, play a key role in the regulation of neuroplasticity associated with learning and memory, neuronal degeneration, chronic pain and mental disorders, we have made effort to investigate the structure, function and regulation of NMDA receptor signaling complex. The NMDA receptor can be sub-classified by the cloning of cDNAs as NR1, NR2A-D, NR3 subunits. Functional NMDA receptors in the CNS may exist as a tetramer, containing at least two NR1 and two NR2 subunits The NR1 subunit has at least 8 splice variants (including NR1-1a, -2a, 3a, 4a, with C1 and/or C2 segments deleted in the carboxyl-terminal; NR1-1b, 2b, 3b, 4b with an amino-terminal insertion), and is necessary for every functional NMDA receptor. NR2 subunit subtypes in the receptor assembly varies depending upon the region of the CNS, consequently further increasing the possibilities for receptor diversity. Each NMDA receptor subunit contains a long extracellular amino (N-) terminus that functions in ligand binding, a carboxyl terminal tail (C-tail) on the intracellular aspect of the cytoplasmic membrane and four membrane associated regions.
Current Projects
Identifying the organization of NMDA receptor associated protein tyrosine kinase/phosphatase complex Investigating protein kinase-phosphatase signaling complex in transducing pain signals. Characterizing functional interactions of intracellular sodium and calcium in mediating cross-talk between NMDA receptors In these projects, we apply multiple techniques including protein-binding assay in-vitro, immunoprecipitation assay in non-neuronal expression systems and brain tissues to identify novel protein-protein interactions and critical protein interaction sites. Electrophysiological recordings are conducted to determine potential therapeutic effects of novel protein interactions identified in our biochemical experiments at single-channel and whole-cell levels in non-neuronal express system, cultured central neurons and brain slices. Fluorescence image techniques are also unutilized to investigate protein translocation, alteration of intracellular ions and neuronal morphology.
Current Laboratory Members
Mohammad K. Ali Ph.D., Aligarh Muslim University, 1999 Post-doctoral research fellow Hai-Fa Qiao M.D. Shandong University of Traditional Chinese Medicine, 1996 Post-doctoral research fellow Vedrana Marin Ph.D., Florida State University, 2005 Post-doctoral research fellow Yu-Feng Xie Ph.D., Medical School, Xi’an Jiaotong University, 2004 Post-doctoral research fellow Shuangxiu Lin B.A. Xuzhou Teachers’ College, 1977 Laboratory Technician Chun L. Kwan: M.Sc. University of Toronto, ‘94 Laboratory Technician Jindong Xu: B.M. Tongji Medical University, 95 Graduate Student, Neuroscience NMDA receptor complex
Selected References
Yu, X. M. and Mense, S.: Response properties and descending control of rat dorsal horn neurones with deep receptive fields. Neuroscience 1990 (39) 823 831. Yu, X.-M., Sessle, B.J., Haas, D.A., Izzo, A., Vernon, H. and Hu, J.W.: Involvement of NMDA receptor mechanisms in jaw electromyographic activity and plasma extravasation induced by inflammatory irritant application to temporomandibular joint region of rats. Pain 1996 (68) 179-181. Yu, X.-M., Askalan, R., Keil II, G.L. and Salter, M.W.: NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 1997 (275) 674-678. Yu, X.-M. and Salter, M.W.: The gain control of NMDA receptor mediated synaptic currents by intracellular sodium. Nature 1998 (396) 469-474. Yu, X.-M. , and Salter, M.W.: Src, a novel molecular switch governing the gain of synaptic transmission mediated by NMDA receptors. Proc. Natl. Acad. Sci. USA, 1999, (96) 7697-7704. Liu, F., Wan Q., Pristupa, Z.B. Yu, X.-M., Wang, Y.T. and Niznik, H.B.: Direct protein-protein coupling enables cross-talk between dopamine D5 and -aminobutyric acid A receptors. Nature 2000 (403) 274-280. Lee, F.J., Xue, S., Pei, L., Vukusic, B., Chéry, N., Wang, Y., Wang, Y.T., Niznik, H.B. Yu, X.-M., and Liu, F.: Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell 2002 (111) 219-230. Lei, G., Xue, S., Chéry, N., Liu, Q., Xu, J.-D., Kwan, C.L., Fu, Y.P., Lu, Y.M., Liu, M.Y., Harder, K.W., and Yu, X.-M.: Gain control of N-methyl-D-aspartate receptor activity by receptor-like protein tyrosine phosphatase alpha. EMBO J. 2002 (21) 2977-2989. Xin, W.-K., Zhao, X.-H., Xu, J., Kwan, C.L., Zhu, K.-M., Cho, J.S.N., Duff, M., Ellen, R.P., McCulloch, C.A.G. and Yu, X.-M.: A Novel Mechanism Underlying the Recruitment of N- Methyl-D-Aspartate Receptors in Neurotoxicity. European J. Neuroscience. 2005 (21) 622-636. Xin, W.-K., Kwan, C.L., Zhao, X.-H., Xu, J., Ellen, R.P., McCulloch, C.A.G. and Yu, X.-M.: A functional interaction of sodium and calcium in the regulation of NMDA receptor activity by remote NMDA receptors. J. Neuroscience. 2005 (25) 139-148. Yu, X.-M.: The role of intracellular sodium (Na+) in the regulation of NMDA receptor-mediated channel activity and toxicity. Molecular Neurobiology 2006, (33) 63-79.