RESEARCH INTERESTS

Molecular mechanisms of ion channel function. Using novel fluorescence techniques in combination with electrophysiology, molecular biology, and biochemistry to better understand ion channel structure and its dynamic rearrangements that underlie channel function in cellular signal transduction.


RESEARCH SYNOPSIS

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.

SELECTED PUBLICATIONS

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 Pub Link

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. Pub Link



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 Pub Link

Cheng, W., and J. Zheng (2006) Applying fluorescence resonance energy transfer (FRET) techniques in live cells studies, Trends in Neurosciences [Chinese], 4, 562-570 Pub Link

Takanishi, C.L., E. Bykova, W. Cheng, and J. Zheng (2006) Quantification of GFP-based FRET in transfected cells, Brain Research, 1091(1), 132-139 Pub Link

Zheng, J. (2006) Patch fluorometry: shedding new light on ion channels, Physiology, 21, 6-12 Pub Link

Zheng, J. (2006) Spectroscopy-based quantitative fluorescence resonance energy transfer analysis, Methods in Molecular Biology, 337, 65-78 Pub Link

Zheng, J. and W.N. Zagotta (2004), Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels, Neuron, 42, 411-421 Pub Link

Zheng, J., M.D. Varnum, and W.N. Zagotta (2003) Disruption of an intersubunit interaction underlies Ca2+-calmodulin modulation of cyclic nucleotide-gated channels, Journal of Neuroscience, 23(22), 8167-8175 Pub Link

Zheng, J., and W.N. Zagotta (2003) Patch-clamp fluorometry recording of conformational rearrangements of ion channels, Science's STKE, pl7 Pub Link

Physiology and Membrane Biology
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