Jaepyo Jeon, PhD
- Instructor, Research Track
ContactJaepyo Jeon, PhD
- Postdoctoral Fellow
- McGovern Medical School, The University of Texas Health Science Center Houston, 2019
- Seoul National University College of Medicine, 2012
Areas of Interest
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.
- Biochem J. May 15;473(10):1379-90. doi: 10.1042/BCJ20160214. Epub 2016 Mar 17. PubMed PMID: 26987813; PubMed Central PMCID: PMC5146954. Regulator of G-protein signaling and GoLoco proteins suppress TRPC4 channel function via acting at Gαi/o.
- roc Natl Acad Sci U S A. Jan 26;113(4):1092-7. doi: 10.1073/pnas.1522294113. Epub 2016 Jan 11. PubMed PMID: 26755577; PubMed Central PMCID: PMC4743816. Critical roles of Gi/o proteins and phospholipase C-δ1 in the activation of receptor-operated TRPC4 channels. P
- Am J Physiol Cell Physiol. Jun 1;308(11):C879-89. doi: 10.1152/ajpcell.00374.2014. Epub 2015 Mar 18. PubMed PMID: 25788576. Close spatio-association of the transient receptor potential canonical 4 (TRPC4) channel with Gαi in TRPC4 activation process.
- Cell Calcium. Oct;54(4):307-19. doi: 10.1016/j.ceca.2013.07.006. Epub 2013 Aug 14. PubMed PMID: 24011658. Activation of TRPC4β by Gαi subunit increases Ca2+ selectivity and controls neurite morphogenesis in cultured hippocampal neuron.
- Kim J, Kwak M, Jeon JP, Myeong J, Wie J, Hong C, Kim SY, Jeon JH, Kim HJ, So I. (2014). Isoform- and receptor-specific channel property of canonical transient receptor potential (TRPC)1/4 channels. Pflugers Arch.; 466(3):491-504. doi: 10.1007/s00424-013-1332-y. Epub 2013 Aug 16. PubMed PMID: 23948741.
- Park SH, Ryu1 SY, Yu WJ, Han YE, Ji YS, Oh K, Sohn JW, Lim A, Jeon JP, Lee H, Lee KH, Lee SH, Berggren PO, Jeon JH, Ho WK. (2013). Leptin promotes KATP channel trafficking by AMPK signaling in pancreatic β-cells. Proc Natl Acad Sci U S A. Jul 30;110(31):12673-8.
- Kim H, Jeon JP, Hong C, Kim J, Myeong J, Jeon JH, So I. (2013). An essential role of PI(4,5)P(2) for maintaining the activity of the transient receptor potential canonical (TRPC)4β. Pflugers Arch. July; 465(7):1011-21. doi: 10.1007/s00424-013-1236-x. Epub 2013 Feb 17.
- Channels (Austin). Sep-Oct;6(5):333-43. doi: 10.4161/chan.21198. Epub 2012 Aug 10. Review. PubMed PMID: 22878724; PubMed Central PMCID: PMC3508772. *equally contributed The roles of G proteins in the activation of TRPC4 and TRPC5 transient receptor potential channels.
- Hong C, Kim J, Jeon JP, Wie J, Kwak M, Ha K, Kim H, Myeong J, Kim SY, Jeon JH, So I. (2012). Gs cascade regulates canonical transient receptor potential 5 (TRPC5) through cAMP mediated intracellular Ca2+ release and ion channel trafficking. Biochem Biophys Res Commun.; 421(1):105-11.
- Jeon JP*, Hong C*, Park EJ, Jeon JH, Cho NH, Kim IG, Choe H, Muallem S, Kim HJ, So I. (2012). Selective Gαi subunits as novel direct activators of transient receptor potential canonical (TRPC)4 and TRPC5 channels. J Biol Chem.; 287(21):17029-39. *: equally contributed.
- Sung TS*, Jeon JP*, Kim BJ*, Hong C, Kim SY, Kim J, Jeon JH, Kim HJ, Suh CK, Kim SJ, So I. (2011). Molecular determinants of PKA-dependent inhibition of TRPC5 channel. Am J Physiol Cell Physiol.; 301(4):C823-32. *: equally contributed.
- Sung TS, Kim MJ, Hong S, Jeon JP, Kim BJ, Jeon JH, Kim SJ, So I. (2009). Functional characteristics of TRPC4 channels expressed in HEK 293 cells. Mol Cells. 27(2):167-73.
- Jeon JP, Lee KP, Park EJ, Sung TS, Kim BJ, Jeon JH, So I. (2008). The specific activation of TRPC4 by Gi protein subtype. Biochem Biophys Res Commun. 377(2):538-43.
- Kim MJ, Jeon JP, Kim HJ, Kim BJ, Lee YM, Choe H, Jeon JH, Kim SJ, So I. (2008). Molecular determinant of sensing extracellular pH in classical transient receptor potential channel 5. Biochem Biophys Res Commun. 365(2):239-45.