Thomas Jefferson University - Ji-Fang Zhang
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Ji-Fang Zhang
Physiology
Thomas Jefferson University
Jefferson Medical College
Department of Molecular Physiology & Biophysics
Associate Professor of Physiology
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Mailing Address
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1020 Locust Street
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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My lab is interested in voltage-gated Ca2+ channels (VGCCs) and Ca2+ influx in neuronal signaling, in particular, how Ca2+ influx through different types Ca2+ channels is able to specifically initiate/regulate different signaling pathways. We have focused on identification and functional characterization of novel Ca2+ channel partner proteins and their roles in Ca2+-dependent signaling in neurons. These novel Ca2+ channel partner proteins were identified by yeast two-hybrid screening using the C-termini of three different types of VGCCs. biochemical and functional characterization of these novel Ca2+ channel partner proteins are in progress using combined approaches of molecular biology, biochemistry, cell biology, electrophysiology and fluorescence imaging. In particular, we are focusing on the following areas:
(1) Ca2+ channels and Ca2+ influx in regulating synaptic vesicle recycling. We will continue to address the role of Ca2+ channels and Ca2+ influx in vesicular endocytosis. (a) Identifying all amino acid residues which form the Ca2+ sensor; (b) examining the enzymatic activities of endophilin at different Ca2+ levels; and (c) examining the effects of dominant negative constructs on hippocampal neurons to see how Ca2+ regulates vesicle endocytosis. (d) solving the crystal structures of the novel Ca2+ sensor. In addition to endophilin, we have identified several other proteins which are implicated in synaptic vesicle recycling.
(2) Roles of motor protein subunits in determining sorting and trafficking of different types of Ca2+ channels. We will continue to examine interactions between motor proteins and Ca2+ channels; particularly focusing on (a) how such interactions can be regulated, e.g. phosphorylation, (b) how such interactions may contribute to synaptogenesis; and (c) potential roles of these interactions in synaptic plasticity.
(3) The unique roles of Ca2+ channels and Ca2+ influx in regulation of gene expression, particularly in synaptic plasticity and in certain forms of neurodegeneration. We will focus on several proteins we identified during yeast two-hybrid screening. These proteins are known to be involved in regulation of gene expression. We will test whether interactions of these proteins with Ca2+ channels contribute to activity-dependent regulation of gene expression in neurons. Mutations in P/Q-type Ca2+ channels, particularly in the channel C-terminus, have been implicated in neurodegeneration, as well as diseases such as certain forms of epilepsy, migraines and ataxia. Defects in P/Q-type Ca2+ channels cannot be compensated by other types of Ca2+ channels. We want to test the hypothesis that P/Q type Ca2+ channel mutations alter the Ca2+-dependent signaling process and consequently lead to neurodegeneration.
(4) Modulation of Ca2+ channel activities though specific signaling complex. We will continue to examine the dynamics of the PKC signaling complex, and how formation of this complex is regulated by physiological factors; particularly (a) effects of phosphorylation by PKC on the formation of the complex; and (b) how phosphatase fits into complex.
The research activities in my lab are currently supported by grants from NIMH and NINDS of the National Institutes of Health.
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Keywords
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Ion channels, voltage-gated calcium channels; calcium signaling; signal transduction
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Publications
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- Chen, Y., Lai, M., Maeno-Hikichi, Y. & Zhang J.F. Essential role of the LIM domain in formation of the PKCe-ENH-N-type Ca2+ channel complex. Cellular Signalling, 18:215-224, February 2006.
- Ahern, C.A., Zhang, J.F., Wookalis, M.J. & Horn, R. Modulation of the cardiac sodium channel NaV1.5 by Fyn, a Src family tyrosine kinase. Circulation Research, 96:989-996, May 2005.
- Lai, M., Wang, F., Rohan, J.G., Maeno-Hikichi, Y., Chen, Y., Zhou, Y., Gao, G., Sather, W.A. & Zhang, J.F. (2005) A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons. Nature Neuroscience, 8:435-444, April 2005.
- Li D., Wang F., Lai M., Chen, Y. & Zhang, J.F. A PP2ca-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by PKC. Journal of Neuroscience, 25:1914-1923, Febuary, 2005.
- Chen Y, Deng L, Maeno-Hikichi Y, Lai M, Chang S, Chen G, Zhang JF. Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis. Cell, 115:37-48, October 2003.
- Maeno-Hikichi, Y., Chang, S., Matsumura, K., Lai, M., Lin, H., Nakagawa, N., Kuroda, S. & Zhang, J.F. A PKCe-ENH-channel complex specifically modulates N-type Ca2+ channels. Nature Neuroscience, 6:468-475, May 2003.
- Zhang, J.F., P.T. Ellinor, Aldrich, R.W. & Tsien, R.W. Multiple structural elements in voltage dependent calcium channels support their inhibition by G proteins. Neuron, 17:991-1003, November 1996.
- Tsien, R.W., Ellinor, P.T., Zhang, J.F., Bezprozvanny, I. Molecular biology of calcium channels and structural determinants of key functions. Journal of Cardiovascular Pharmacology, 27A:S4-S10, 1996.
- Ellinor, P.T., Yang, J., Sather, W.A., Zhang, J.F. & Tsien, R.W. Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions. Neuron, 15:1121-1132, November, 1995.
- Sather, W.A., Tanabe, T., Zhang, J.F. & Tsien, R.W. Biophysical and pharmacological characterization of a class A calcium channel. Annals of New York Academy of Science, 747:294-301, December 1994.
- Ellinor, P.T., Zhang, J.F., Horne, W.A., Tsien, R.W. Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin. Nature, 372:272-275, November 1994.
- Zhang, J.F., P.T. Ellinor, Aldrich, R.W. & Tsien, R.W. Molecular determinants of voltage-dependent inactivation in calcium channels. Nature, 372:97-100, November 1994.
- Zhang, J.F., Randall, A.D., Ellinor, P.T., Horne, W.A., Sather, W.A., Tanabe, T., Schwarz, T.L. & Tsien, R.W. Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacology, 32:1075-1088, November, 1993.
- Yang, J., Ellinor, P.T., Sather, W.A., Zhang, J.F. & Tsien, R.W. Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. Nature, 366:158-161, November 1993.
- Sather, W.A., Tanabe, T., Zhang, J.F., Mori, Y., Adams, M.E. & Tsien, R.W. Distinctive biophysical and pharmacological properties of class A (BI) calcium channel a1 subunits. Neuron, 11:291-303, August 1993.
- Ellinor, P.T., Zhang, J.F., Randall, A.D., Zhou, M., Schwarz, T.L., Tsien, R.W. & Horne, W.A. Functional expression of a rapidly inactivating neuronal calcium channel. Nature, 363:455-458, June 1993
- Zhang, J.F., Robinson, R.B., Siegelbaum, S.A. Sympathetic neurons mediate developmental change in cardiac sodium channel gating through long-term neurotransmitter action. Neuron, 9:97-103, July 1992.
- Zhang, J.F. & Siegelbaum, S.A. Effects of external protons on the cardiac sodium channels from guinea pig. Journal of General Physiology, 98:1065-1083, December 1991.
- Steinberg, S.F., Kaplan, L.M., Inouye, T., Zhang, J.F. & Robinson, R.B. Alpha-1 adrenergic stimulation of 1,4,5-inositol trisphosphate formation in ventricular myocytes. Journal of Pharmacology and Experimental Therapeutics, 250:1141-1148, September 1989.
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Individual Expertise profile of
Ji-Fang Zhang, Copyright © Ji-Fang Zhang.
Last Updated
by Ji-Fang Zhang : Monday, November 13, 2006 12:22:10 PM
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