Molecular mechanisms of ion channel function. Using novel fluorescence techniques in the combination with electrophysiology, molecular biology, and biochemistry to better understand ion channel structure and its dynamic rearrangements the underlie channel function in cellular signal transduction.
Ion channels form the basis of electrical excitability of neurons and muscle cells. In response to specific electrical or chemical stimuli, these membrane proteins open a pathway across the cell membrane for selected ions, causing changes in membrane potential or intracellular levels of calcium. Activation of an ion channel is under extremely precise control that allows highly specialized processes, e.g., photoreceptor cells to detect the presence of a single photon. Research in my laboratory focuses on the protein structures critical for channel organization, activation, and modulation. The moving parts of the channel are labeled with fluorophores that serve as a molecular sensor for local conformational rearrangements. Recording the fluorescence emission let us directly observe channel structural changes in real time under physiological conditions. The same population of channels is simultaneously monitored with patch-clamp recordings so that we can correlate structure changes to the channel's function states. In particular, we use Fluorescence Resonance Energy Transfer (FRET) to measure atomic distances between channel structures.
Qiu, S., X.-M. Zhang, J.-Y. Cao, W. Yang, Y.-G. Yan, L. Shan, J. Zheng, and J.-H. Luo (2009) An ER retention signal located in the extracellular amino-terminal domain of NR2A subunit of NMDA receptors, Journal of Biological Chemistry, 284:20285-20298
Qu, Z., W. Cheng, Y. Cui, Y. Cui, and J. Zheng (2009) Human disease-causing mutations disrupt an N-C terminal interaction and channel function of bestrophin 1, Journal of Biological Chemistry, 284:16473-16481.
Sun, P., J. Wang, W. Gu, W. Cheng, G.-Z. Jin, E. Friedman, J. Zheng, and X. Zhen (2009) PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation, Cell Research 19:612-624.
Liang, S.-S., F. Yang, C. Zhou, Y. Wang, S. Li, C.K. Sun, J.L. Puglisi, D. Bers, C. Sun, and J. Zheng (2009) Temperature-dependent activation of neurons by continuous near-infrared laser, Cell Biochemistry and Biophysics, 53(1), 33-42.
Zheng, J., and K. Matulef (2009) Cyclic nucleotide-gated ion channels, In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester.
Zheng, J. (2009) FRET and its biological application as a molecular ruler, in Handbook of Modern Biophysics, Vol. 3: Biomedical Applications in Biophysics, Humana Press.
Bykova, E.A. and J. Zheng (2009) Spectra FRET, a fluorescence resonance energy transfer method in live cells, Annual Reviews in Fluorescence 2007, Chapter 4, Springer.
Zheng, J. (2008) Patch fluorometry, In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester.
Chen, T.Y., Y.F. Lin, and J. Zheng (2008) Electrophysiological measurements of membrane proteins, in Handbook on Biophysics, Vol. 1, Chapter 5, Humana Press.
Vetter, I., W. Cheng, M. Peiris, B.D. Wyse, S.J. Roberts-Thomson, J. Zheng, G.R. Monteith, P.J. Cabot (2008) Rapid, opioid-sensitive mechanisms involved in transient receptor potential vanilloid 1 sensitization, Journal of Biological Chemistry, 283, 19540-19550.
Ying, G., S.S. Liu, S. Qiu, W. Cheng, J. Zheng, J.H. Luo (2007) Fluorescence resonance energy transfer analysis of subunit assembly of the ASIC channel, Biochemical and Biophysical Research Communications, 359, 143-150.
Cheng, W., F. Yang, C.L. Takanishi, and J. Zheng (2007) Thermosensitive TRPV Channel Subunits Co-assemble into Heteromeric Channels with Intermediate Conductance and Gating Properties, Journal of General Physiology, 129, 191-207. Featured on the cover.
Zheng, J. (2006) Patch fluorometry: shedding new light on ion channels, Physiology, 21, 6-12.
Cheng, W., and J. Zheng (2006) Applying fluorescence resonance energy transfer (FRET) techniques in live cells studies, Trends in Neurosciences [Chinese], 4, 562-570.
Zheng, J. (2006) Spectroscopy-based quantitative fluorescence resonance energy transfer analysis, Methods in Molecular Biology, 337, 65-78.
Bykova, E.A., X.D. Zhang, T.Y. Chen, and J. Zheng (2006) Large movement in the C terminus of CLC-0 chloride channel during slow gating, Nature Structural and Molecular Biology, 13, 1115-1119.
Takanishi, C.L., E.A. Bykova, W. Cheng, and J. Zheng (2006) Quantification of GFP-based FRET in live cells, Brain Research, 1091(1), 132-139.
Zheng, J. and W.N. Zagotta (2004), Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels, Neuron, 42, 411-421.
Faculty