The Korean Journal of Physiology and Pharmacology

  • 제23권3호
  • /
  • Pages.191-201
  • /
  • 2019
  • /
  • 1226-4512(pISSN)
  • /
  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
권호 표지
DOI QR코드

DOI QR Code

Englerin A-sensing charged residues for transient receptor potential canonical 5 channel activation

  • Jeong, SeungJoo (Department of Physiology, Seoul National University College of Medicine) ;
  • Ko, Juyeon (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Minji (College of Veterinary Medicine, Chungnam National University) ;
  • Park, Ki Chul (Department of Bioinformatics, Korea University) ;
  • Park, Eunice Yon June (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Jinsung (Department of Physiology, Seoul National University College of Medicine) ;
  • Baik, Youngjoo (Department of Physiology, Seoul National University College of Medicine) ;
  • Wie, Jinhong (Department of Biology, University of Pennsylvania) ;
  • Cho, Art E. (Department of Bioinformatics, Korea University) ;
  • Jeon, Ju-hong (Department of Physiology, Seoul National University College of Medicine) ;
  • So, Insuk (Department of Physiology, Seoul National University College of Medicine)
  • 투고 : 2018.10.09
  • 심사 : 2019.03.26
  • 발행 : 2019.05.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or $GTP{\gamma}S$. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.

키워드

참고문헌

  1. Kim MJ, Jeon JP, Kim HJ, Kim BJ, Lee YM, Choe H, Jeon JH, Kim SJ, So I. Molecular determinant of sensing extracellular pH in classical transient receptor potential channel 5. Biochem Biophys Res Commun. 2008;365:239-245. https://doi.org/10.1016/j.bbrc.2007.10.154
  2. Hong C, Kwak M, Myeong J, Ha K, Wie J, Jeon JH, So I. Extracellular disulfide bridges stabilize TRPC5 dimerization, trafficking, and activity. Pflugers Arch. 2015;467:703-712. https://doi.org/10.1007/s00424-014-1540-0
  3. Jeon JP, Roh SE, Wie J, Kim J, Kim H, Lee KP, Yang D, Jeon JH, Cho NH, Kim IG, Kang DE, Kim HJ, So I. Activation of $TRPC4{\beta}$ by $G{\alpha}_{i}$ subunit increases $Ca^{2+}$ selectivity and controls neurite morphogenesis in cultured hippocampal neuron. Cell Calcium. 2013;54:307-319. https://doi.org/10.1016/j.ceca.2013.07.006
  4. Venkatachalam K, Zheng F, Gill DL. Regulation of canonical transient receptor potential (TRPC) channel function by diacylglycerol and protein kinase C. J Biol Chem. 2003;278:29031-29040. https://doi.org/10.1074/jbc.M302751200
  5. Sukumar P, Beech DJ. Stimulation of TRPC5 cationic channels by low micromolar concentrations of lead ions ($Pb^{2+}$). Biochem Biophys Res Commun. 2010;393:50-54. https://doi.org/10.1016/j.bbrc.2010.01.074
  6. Hong C, Seo H, Kwak M, Jeon J, Jang J, Jeong EM, Myeong J, Hwang YJ, Ha K, Kang MJ, Lee KP, Yi EC, Kim IG, Jeon JH, Ryu H, So I. Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington's disease. Brain. 2015;138:3030-3047. https://doi.org/10.1093/brain/awv188
  7. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y. Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol. 2006;2:596-607. https://doi.org/10.1038/nchembio821
  8. Zhu MH, Chae M, Kim HJ, Lee YM, Kim MJ, Jin NG, Yang DK, So I, Kim KW. Desensitization of canonical transient receptor potential channel 5 by protein kinase C. Am J Physiol Cell Physiol. 2005;289:C591-C600. https://doi.org/10.1152/ajpcell.00440.2004
  9. Akbulut Y, Gaunt HJ, Muraki K, Ludlow MJ, Amer MS, Bruns A, Vasudev NS, Radtke L, Willot M, Hahn S, Seitz T, Ziegler S, Christmann M, Beech DJ, Waldmann H. (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angew Chem Int Ed Engl. 2015;54:3787-3791. https://doi.org/10.1002/anie.201411511
  10. Beck A, Speicher T, Stoerger C, Sell T, Dettmer V, Jusoh SA, Abdulmughni A, Cavalie A, Philipp SE, Zhu MX, Helms V, Wissenbach U, Flockerzi V. Conserved gating elements in TRPC4 and TRPC5 channels. J Biol Chem. 2013;288:19471-19483. https://doi.org/10.1074/jbc.M113.478305
  11. Ko J, Myeong J, Yang D, So I. Calcium permeability of transient receptor potential canonical (TRPC) 4 channels measured by TRPC4-GCaMP6s. Korean J Physiol Pharmacol. 2017;21:133-140. https://doi.org/10.4196/kjpp.2017.21.1.133
  12. Rodrigues T, Sieglitz F, Somovilla VJ, Cal PM, Galione A, Corzana F, Bernardes GJ. Unveiling (-)-englerin A as a modulator of L-type calcium channels. Angew Chem Int Ed Engl. 2016;55:11077-11081. https://doi.org/10.1002/anie.201604336
  13. Okada T, Shimizu S, Wakamori M, Maeda A, Kurosaki T, Takada N, Imoto K, Mori Y. Molecular cloning and functional characterization of a novel receptor-activated TRP $Ca^{2+}$ channel from mouse brain. J Biol Chem. 1998;273:10279-10287. https://doi.org/10.1074/jbc.273.17.10279
  14. Jung S, Muhle A, Schaefer M, Strotmann R, Schultz G, Plant TD. Lanthanides potentiate TRPC5 currents by an action at extracellular sites close to the pore mouth. J Biol Chem. 2003;278:3562-3571. https://doi.org/10.1074/jbc.M211484200
  15. Gross SA, Guzman GA, Wissenbach U, Philipp SE, Zhu MX, Bruns D, Cavalie A. TRPC5 is a $Ca^{2+}$-activated channel functionally coupled to $Ca^{2+}$-selective ion channels. J Biol Chem. 2009;284:34423-34432. https://doi.org/10.1074/jbc.M109.018192
  16. Philipp S, Cavalie A, Freichel M, Wissenbach U, Zimmer S, Trost C, Marquart A, Murakami M, Flockerzi V. A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL. EMBO J. 1996;15:6166-6171. https://doi.org/10.1002/j.1460-2075.1996.tb01004.x
  17. Gees M, Colsoul B, Nilius B. The role of transient receptor potential cation channels in $Ca^{2+}$ signaling. Cold Spring Harb Perspect Biol. 2010;2:a003962. https://doi.org/10.1101/cshperspect.a003962
  18. Ludlow MJ, Gaunt HJ, Rubaiy HN, Musialowski KE, Blythe NM, Vasudev NS, Muraki K, Beech DJ. (-)-Englerin A-evoked cytotoxicity is mediated by Na+ influx and counteracted by $Na^{+}/K^{+}$-ATPase. J Biol Chem. 2017;292:723-731. https://doi.org/10.1074/jbc.M116.755678
  19. Muraki K, Ohnishi K, Takezawa A, Suzuki H, Hatano N, Muraki Y, Hamzah N, Foster R, Waldmann H, Nussbaumer P, Christmann M, Bon RS, Beech DJ. $Na^{+}$ entry through heteromeric TRPC4/C1 channels mediates (-)Englerin A-induced cytotoxicity in synovial sarcoma cells. Sci Rep. 2017;7:16988. https://doi.org/10.1038/s41598-017-17303-3
  20. Duan J, Li J, Zeng B, Chen GL, Peng X, Zhang Y, Wang J, Clapham DE, Li Z, Zhang J. Structure of the mouse TRPC4 ion channel. Nat Commun. 2018;9:3102. https://doi.org/10.1038/s41467-018-05247-9
  21. Vinayagam D, Mager T, Apelbaum A, Bothe A, Merino F, Hofnagel O, Gatsogiannis C, Raunser S. Electron cryo-microscopy structure of the canonical TRPC4 ion channel. Elife. 2018;7. pii: e36615.
  22. Semtner M, Schaefer M, Pinkenburg O, Plant TD. Potentiation of TRPC5 by protons. J Biol Chem. 2007;282:33868-33878. https://doi.org/10.1074/jbc.M702577200
  23. Carson C, Raman P, Tullai J, Xu L, Henault M, Thomas E, Yeola S, Lao J, McPate M, Verkuyl JM, Marsh G, Sarber J, Amaral A, Bailey S, Lubicka D, Pham H, Miranda N, Ding J, Tang HM, Ju H, et al. Englerin A agonizes the TRPC4/C5 cation channels to inhibit tumor cell line proliferation. PLoS One. 2015;10:e0127498. https://doi.org/10.1371/journal.pone.0127498
  24. Rubaiy HN, Seitz T, Hahn S, Choidas A, Habenberger P, Klebl B, Dinkel K, Nussbaumer P, Waldmann H, Christmann M, Beech DJ. Identification of an (-)-englerin A analogue, which antagonizes (-)-englerin A at TRPC1/4/5 channels. Br J Pharmacol. 2018;175:830-839. https://doi.org/10.1111/bph.14128
  25. Chen X, Li W, Riley AM, Soliman M, Chakraborty S, Stamatkin CW, Obukhov AG. Molecular determinants of the sensitivity to $G_{q/11}$-phospholipase C-dependent gating, $Gd^{3+}$ potentiation, and $Ca^{2+}$ permeability in the transient receptor potential canonical type 5 (TRPC5) channel. J Biol Chem. 2017;292:898-911. https://doi.org/10.1074/jbc.M116.755470
  26. Duan J, Li J, Chen GL, Xie K, Peng X, Zhou W, Zhong J, Zhang Y, Xu J, Xue C, Zhu L, Liu W, Tian XL, Wang J, Zeng B, Clapham DE, Li Z, Zhang J. Cryo-EM structure of the receptor-activated TRPC5 ion channel at 2.9 angstrom resolution. bioRxiv. 2018;2018:467969.
  27. Li J, Zhang X, Song X, Liu R, Zhang J, Li Z. The structure of TRPC ion channels. Cell Calcium. 2019;80:25-28. https://doi.org/10.1016/j.ceca.2019.03.005
  28. Kim H, Kim J, Jeon JP, Myeong J, Wie J, Hong C, Kim HJ, Jeon JH, So I. The roles of G proteins in the activation of TRPC4 and TRPC5 transient receptor potential channels. Channels (Austin). 2012;6:333-343. https://doi.org/10.4161/chan.21198

피인용 문헌

  1. Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition vol.11, pp.9, 2020, https://doi.org/10.1021/acsmedchemlett.0c00186