Philadelphia University + Thomas Jefferson University

Zhang, Ji-fang

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Ji-fang Zhang, PhD

Contact Dr. Zhang

900 Walnut Street
JHN 4th floor
Philadelphia, PA 19107

(215) 503-5669
(215) 503-4358 fax

Research and Clinical Interests

Voltage-gated calcium channels, calcium signaling in neurons

My lab is interested in voltage-gated Ca2+ channels (VGCCs) and Ca2+ influx through VGCCs in neuronal signaling. The particular question we ask is how Ca2+ influx through different types VGCCs can specifically initiate/regulate different signaling pathways. We have focused on identification and functional characterization of novel Ca2+ channel partner proteins in neurons. The current projects include:

(1) VGCCs and Ca2+ influx in synaptic vesicle (SV) recycling. Ca2+ influx through VGCCs is essential for release of neurotransmitters. Ca2+ has also been implicated in regulation of SV endocytosis. However, the mechanisms for such regulation are not clear. We have identified a novel Ca2+ sensor in endophilin, a protein important for SV endocytosis (Cell, 2003). Binding of Ca2+ to endophilin changes its conformation and may contribute to regulation of SV endocytosis by Ca2+. Experiments are in progress to address (a) the molecular and structural nature of the novel Ca2+ sensor; and (b) the functional roles of this novel Ca2+ sensor in regulation of SV endocytosis.

(2) Distribution and trafficking of VGCCs. Different types of VGCCs have their unique subcellular distributions in neurons. Little is known of the molecular mechanisms for such distribution. We have shown that a novel VGCC partner protein, tctex1, a motor protein subunit, plays an important role in channel trafficking (Nature Neuroscience, 2005). We will continue to examine interactions between motor proteins and VGCCs; particularly focusing on (a) how such interactions can be regulated; and (b) whether such interactions may contribute to synaptogenesis.

(3) VGCCs and Ca2+ influx in regulation of gene expression, particularly in synaptic plasticity and in neurodegeneration. We will focus on several proteins, which are known to be involved in regulation of gene expression. We will test whether interactions of these proteins with VGCCs contribute to activity-dependent regulation of gene expression in neurons. The techniques that I use in my research are molecular biology, biochemistry, cell biology, electrophysiology and fluorescence imaging. Knowledge from our research will help understand the fundamentals of neurobiology and shed light on why genetic defects of VGCCs may cause certain neurological diseases.

Publications

Most Recent Peer-Reviewed Publications

  1. Selective phosphorylation modulates the PIP 2 sensitivity of the CaM-SK channel complex
  2. Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca2+-sensing and SK channel activation
  3. Characterization of two distinct modes of endophilin in clathrin-mediated endocytosis
  4. Identification of the functional binding pocket for compounds targeting small-conductance Ca 2+ -activated potassium channels
  5. Structural basis for calmodulin as a dynamic calcium sensor
  6. Reply to PDLIM5 is not a neuronal CaV2.2 adaptor protein
  7. Structure of the SH3 domain of rat endophilin A2
  8. Essential role of the LIM domain in the formation of the PKCε0859-ENH-N-type Ca2+ channel complex
  9. A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons
  10. Modulation of the cardiac sodium channel Nav1.5 by Fyn, a Src family tyrosine kinase
  11. A protein phosphatase 2cα-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C
  12. Formation of an endophilin-Ca2+channel complex is critical for clathrin-mediated synaptic vesicle endocytosis
  13. A PKCε-ENH-channel complex specifically modulates N-type Ca2+ channels
  14. Multiple structural elements in voltage-dependent Ca2+channels support their inhibition by G proteins
  15. Ca2+channel selectivity at a single locus for high-affinity Ca2+interactions
  16. Molecular determinants of voltage-dependent inactivation in calcium channels
  17. Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin
  18. Biophysical and pharmacological characterization of a class A calcium channel
  19. Molecular determinants of Ca2+selectivity and ion permeation in L-type Ca2+channels
  20. Functional expression of a rapidly inactivating neuronal calcium channel