Jaepyo Jeon, PhD

Areas of Interest

Research Interests

G-protein mediated mechanism of TRPC channel activation and their physiological/pathological implications

Transient Receptor Potential Canonical (TRPC) proteins are homologs of Drosophila TRP channel. In mammals, there are seven TRPC members, serving a broad array of physiological and pathophysiological functions in different tissues. TRPC channels are calcium permeable nonselective cation channels. When they are open or activated, sodium and calcium flux into the cell, leading to consequent increases in membrane potential (depolarization) and intracellular calcium concentration. Studies have shown that the opening of the majority of TRPC channels depends on the activation of G protein-coupled receptors that signal through Gq proteins. Recently, we found that for the activation of TRPC4 and TRPC5, both Gq and Gi signaling pathways are involved.

My current research focuses on elucidating the physiological relevance of TRPC4 channels. I have investigated the role of TRPC4 channel in neurons and found that TRPC4 plays an important role in dendritic development of hippocampal neurons via a Gi/Gq-dependent mechanism.

Using advanced fluorescence microscopy superresolution imaging techniques, I have identified a novel role of TRPC4 in regulating dendric growth and stability. This occurs through a fine control of actin cytoskeleton structures via TRPC4 dependent activation of myosin light-chain kinases which helps stabilizing newly developed dendritic branches. These observations demonstrate a new mechanism underlying TRPC4 regulation of actin-cytoskeleton.

In addition to neurodevelopment function of G protein-mediated TRPC4 and other TRPC channel activities, I am also investigating the role of TRPC channels in ischemic neuronal death by excitotoxicity. The ischemic insults to the brain enhance glutamate release to induce membrane depolarization of neurons. TRPC channels can be a potential mediator of membrane excitability caused by metabotropic glutamate receptors capable of stimulating both Gq and Gi signaling pathways in neurons. I found that the genetic ablation of Trpc4 and Trpc1,4,5,6 genes protected brain neurons from injury caused by ischemic stroke. This follows the bases for further mechanistic studies of TRPC-mediated neuronal cell death.

I will extend my research as follows:

• To study the roles of TRPC4 and other TRPC channels in the regulation of cytoskeleton in neuronal and non-neuronal systems.
• To investigate the pathological implications of TRPC channels in stroke and neurological disorders.

Publications

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