DOI QR코드

DOI QR Code

Transient Receptor Potential Cation Channel V1 (TRPV1) Is Degraded by Starvation- and Glucocorticoid-Mediated Autophagy

  • Ahn, Seyoung (Graduate School for Biomedical Science and Engineering, College of Medicine, Hanyang University) ;
  • Park, Jungyun (Graduate School for Biomedical Science and Engineering, College of Medicine, Hanyang University) ;
  • An, Inkyung (Graduate School for Biomedical Science and Engineering, College of Medicine, Hanyang University) ;
  • Jung, Sung Jun (Department of Physiology, College of Medicine, Hanyang University) ;
  • Hwang, Jungwook (Graduate School for Biomedical Science and Engineering, College of Medicine, Hanyang University)
  • 투고 : 2013.12.23
  • 심사 : 2014.02.17
  • 발행 : 2014.03.31

초록

A mammalian cell renovates itself by autophagy, a process through which cellular components are recycled to produce energy and maintain homeostasis. Recently, the abundance of gap junction proteins was shown to be regulated by autophagy during starvation conditions, suggesting that transmembrane proteins are also regulated by autophagy. Transient receptor potential vanilloid type 1 (TRPV1), an ion channel localized to the plasma membrane and endoplasmic reticulum (ER), is a sensory transducer that is activated by a wide variety of exogenous and endogenous physical and chemical stimuli. Intriguingly, the abundance of cellular TRPV1 can change dynamically under pathological conditions. However, the mechanisms by which the protein levels of TRPV1 are regulated have not yet been explored. Therefore, we investigated the mechanisms of TRPV1 recycling using HeLa cells constitutively expressing TRPV1. Endogenous TRPV1 was degraded in starvation conditions; this degradation was blocked by chloroquine (CLQ), 3MA, or downregulation of Atg7. Interestingly, a glucocorticoid (cortisol) was capable of inducing autophagy in HeLa cells. Cortisol increased cellular conversion of LC3-I to LC-3II, leading autophagy and resulting in TRPV1 degradation, which was similarly inhibited by treatment with CLQ, 3MA, or downregulation of Atg7. Furthermore, cortisol treatment induced the colocalization of GFP-LC3 with endogenous TRPV1. Cumulatively, these observations provide evidence that degradation of TRPV1 is mediated by autophagy, and that this pathway can be enhanced by cortisol.

키워드

참고문헌

  1. Ahn, S., Kim, J., and Hwang, J. (2013). CK2-mediated TEL2 phosphorylation augments nonsense-mediated mRNA decay (NMD) by increase of SMG1 stability. Biochim. Biophys. Acta 1829, 1047-1055. https://doi.org/10.1016/j.bbagrm.2013.06.002
  2. Bejarano, E., Girao, H., Yuste, A., Patel, B., Marques, C., Spray, D.C., Pereira, P., and Cuervo, A.M. (2012). Autophagy modulates dynamics of connexins at the plasma membrane in a ubiquitin-dependent manner. Mol. Biol. Cell 23, 2156-2169. https://doi.org/10.1091/mbc.E11-10-0844
  3. Biggs, J.E., Yates, J.M., Loescher, A.R., Clayton, N.M., Boissonade, F.M., and Robinson, P.P. (2007). Changes in vanilloid receptor 1 (TRPV1) expression following lingual nerve injury. Eur. J. Pain 11, 192-201. https://doi.org/10.1016/j.ejpain.2006.02.004
  4. Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., and Julius, D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816-824. https://doi.org/10.1038/39807
  5. Clapham, D.E. (2003). TRP channels as cellular sensors. Nature 426, 517-524. https://doi.org/10.1038/nature02196
  6. Fong, J.T., Kells, R.M., Gumpert, A.M., Marzillier, J.Y., Davidson, M.W., and Falk, M.M. (2012). Internalized gap junctions are degraded by autophagy. Autophagy 8, 794-811. https://doi.org/10.4161/auto.19390
  7. Fukuoka, T., Tokunaga, A., Tachibana, T., Dai, Y., Yamanaka, H., and Noguchi, K. (2002). VR1, but not P2X(3), increases in the spared L4 DRG in rats with L5 spinal nerve ligation. Pain 99, 111-120. https://doi.org/10.1016/S0304-3959(02)00067-2
  8. Gallego-Sandin, S., Rodriguez-Garcia, A., Alonso, M.T., and Garcia-Sancho, J. (2009). The endoplasmic reticulum of dorsal root ganglion neurons contains functional TRPV1 channels. J. Biol. Chem. 284, 32591-32601. https://doi.org/10.1074/jbc.M109.019687
  9. Goswami, C., and Hucho, T. (2007). TRPV1 expression-dependent initiation and regulation of filopodia. J. Neurochem. 103, 1319-1333. https://doi.org/10.1111/j.1471-4159.2007.04846.x
  10. Hudson, L.J., Bevan, S., Wotherspoon, G., Gentry, C., Fox, A., and Winter, J. (2001). VR1 protein expression increases in undamaged DRG neurons after partial nerve injury. Eur. J. Neurosci. 13, 2105-2114. https://doi.org/10.1046/j.0953-816x.2001.01591.x
  11. Hwang, S.W., Cho, H., Kwak, J., Lee, S.Y., Kang, C.J., Jung, J., Cho, S., Min, K.H., Suh, Y.G., Kim, D., et al. (2000). Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc. Natl. Acad. Sci. USA 97, 6155-6160. https://doi.org/10.1073/pnas.97.11.6155
  12. Jia, J., Yao, W., Guan, M., Dai, W., Shahnazari, M., Kar, R., Bonewald, L., Jiang, J.X., and Lane, N.E. (2011). Glucocorticoid dose determines osteocyte cell fate. FASEB J. 25, 3366-3376. https://doi.org/10.1096/fj.11-182519
  13. Jung, J., Shin, J.S., Lee, S.Y., Hwang, S.W., Koo, J., Cho, H., and Oh, U. (2004). Phosphorylation of vanilloid receptor 1 by $Ca^{2+}$/calmodulin-dependent kinase II regulates its vanilloid binding. J. Biol. Chem. 279, 7048-7054. https://doi.org/10.1074/jbc.M311448200
  14. Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., and Yoshimori, T. (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19, 5720-5728. https://doi.org/10.1093/emboj/19.21.5720
  15. Kanai, Y., Nakazato, E., Fujiuchi, A., Hara, T., and Imai, A. (2005). Involvement of an increased spinal TRPV1 sensitization through its up-regulation in mechanical allodynia of CCI rats. Neuropharmacology 49, 977-984. https://doi.org/10.1016/j.neuropharm.2005.05.003
  16. Kedei, N., Szabo, T., Lile, J.D., Treanor, J.J., Olah, Z., Iadarola, M.J., and Blumberg, P.M. (2001). Analysis of the native quarternary structure of vanilloid receptor 1. J. Biol. Chem. 276, 28613-28619. https://doi.org/10.1074/jbc.M103272200
  17. Kim, H.Y., Park, C.K., Cho, I.H., Jung, S.J., Kim, J.S., and Oh, S.B. (2008). Differential changes in TRPV1 expression after trigeminal sensory nerve injury. J. Pain 9, 280-288. https://doi.org/10.1016/j.jpain.2007.11.013
  18. Kim, Y.H., Back, S.K., Davies, A.J., Jeong, H., Jo, H.J., Chung, G., Na, H.S., Bae, Y.C., Kim, S.J., Kim, J.S., et al. (2012). TRPV1 in GABAergic interneurons mediates neuropathic mechanical allodynia and disinhibition of the nociceptive circuitry in the spinal cord. Neuron 74, 640-647. https://doi.org/10.1016/j.neuron.2012.02.039
  19. Lichtenstein, A., Minogue, P.J., Beyer, E.C., and Berthoud, V.M. (2011). Autophagy: a pathway that contributes to connexin degradation. J. Cell Sci. 124, 910-920. https://doi.org/10.1242/jcs.073072
  20. Liu, H., Wang, P., Song, W., and Sun, X. (2009). Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone-mediated autophagy and ubiquitin proteasome pathways. FASEB J. 23, 3383-3392. https://doi.org/10.1096/fj.09-134296
  21. Mathew, R., Karp, C.M., Beaudoin, B., Vuong, N., Chen, G., Chen, H.Y., Bray, K., Reddy, A., Bhanot, G., Gelinas, C., et al. (2009). Autophagy suppresses tumorigenesis through elimination of p62. Cell 137, 1062-1075. https://doi.org/10.1016/j.cell.2009.03.048
  22. Mezey, E., Toth, Z.E., Cortright, D.N., Arzubi, M.K., Krause, J.E., Elde, R., Guo, A., Blumberg, P.M., and Szallasi, A. (2000). Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc. Natl. Acad. Sci. USA 97, 3655-3660. https://doi.org/10.1073/pnas.97.7.3655
  23. Michael, G.J., and Priestley, J.V. (1999). Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. J. Neurosci. 19, 1844-1854.
  24. Mizushima, N., and Komatsu, M. (2011). Autophagy: renovation of cells and tissues. Cell 147, 728-741. https://doi.org/10.1016/j.cell.2011.10.026
  25. Molitoris, J.K., McColl, K.S., Swerdlow, S., Matsuyama, M., Lam, M., Finkel, T.H., Matsuyama, S., and Distelhorst, C.W. (2011). Glucocorticoid elevation of dexamethasone-induced gene 2 (Dig2/RTP801/REDD1) protein mediates autophagy in lymphocytes. J. Biol. Chem. 286, 30181-30189. https://doi.org/10.1074/jbc.M111.245423
  26. Pyo, J.O., Jang, M.H., Kwon, Y.K., Lee, H.J., Jun, J.I., Woo, H.N., Cho, D.H., Choi, B., Lee, H., Kim, J.H., et al. (2005). Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J. Biol. Chem. 280, 20722-20729. https://doi.org/10.1074/jbc.M413934200
  27. Ross, R.A. (2003). Anandamide and vanilloid TRPV1 receptors. Br. J. Pharmacol. 140, 790-801. https://doi.org/10.1038/sj.bjp.0705467
  28. Settembre, C., Fraldi, A., Medina, D.L., and Ballabio, A. (2013). Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat. Rev. Mol. Cell Biol. 14, 283-296. https://doi.org/10.1038/nrm3565
  29. Sugiura, T., Tominaga, M., Katsuya, H., and Mizumura, K. (2002). Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. J. Neurophysiol. 88, 544-548. https://doi.org/10.1152/jn.2002.88.1.544
  30. Szallasi, A., and Blumberg, P.M. (2007). Complex regulation of TRPV1 by vanilloids; in TRP ion channel function in sensory transduction and cellular signaling cascades, Liedtke, W.B. and Heller, S. eds. (Boca Raton (FL)).
  31. Takahata, K., Chen, X., Monobe, K., and Tada, M. (1999). Growth inhibition of capsaicin on HeLa cells is not mediated by intracellular calcium mobilization. Life Sci. 64, PL165-171.
  32. Wallace, A.D., and Cidlowski, J.A. (2001). Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids. J. Biol. Chem. 276, 42714-42721. https://doi.org/10.1074/jbc.M106033200
  33. Wu, Y.T., Tan, H.L., Shui, G., Bauvy, C., Huang, Q., Wenk, M.R., Ong, C.N., Codogno, P., and Shen, H.M. (2010). Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J. Biol. Chem. 285, 10850-10861. https://doi.org/10.1074/jbc.M109.080796
  34. Xia, X., Kar, R., Gluhak-Heinrich, J., Yao, W., Lane, N.E., Bonewald, L.F., Biswas, S.K., Lo, W.K., and Jiang, J.X. (2010). Glucocorticoid-induced autophagy in osteocytes. J. Bone Miner. Res. 25, 2479-2488. https://doi.org/10.1002/jbmr.160

피인용 문헌

  1. TPRV-1 expression in human preeclamptic placenta vol.40, 2016, https://doi.org/10.1016/j.placenta.2016.02.008
  2. Folate deprivation modulates the expression of autophagy- and circadian-related genes in HT-22 hippocampal neuron cells through GR-mediated pathway vol.112, 2016, https://doi.org/10.1016/j.steroids.2016.04.010
  3. Versatile Roles of Intracellularly Located TRPV1 Channel vol.232, pp.8, 2017, https://doi.org/10.1002/jcp.25704
  4. Recent advances in therapeutic strategies that focus on the regulation of ion channel expression vol.160, 2016, https://doi.org/10.1016/j.pharmthera.2016.02.001
  5. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy vol.10, pp.2, 2015, https://doi.org/10.4103/1673-5374.143439
  6. Functional role of TRP channels in modulating ER stress and Autophagy vol.60, pp.2, 2016, https://doi.org/10.1016/j.ceca.2016.02.012
  7. Impact of 60-GHz millimeter waves on stress and pain-related protein expression in differentiating neuron-like cells vol.37, pp.7, 2016, https://doi.org/10.1002/bem.21995
  8. Copper Ion from Cu2O Crystal Induces AMPK-Mediated Autophagy via Superoxide in Endothelial Cells vol.39, pp.3, 2016, https://doi.org/10.14348/molcells.2016.2198
  9. Autophagy exacerbates electrical remodeling in atrial fibrillation by ubiquitin-dependent degradation of L-type calcium channel vol.9, pp.9, 2018, https://doi.org/10.1038/s41419-018-0860-y
  10. Ion channels in the regulation of autophagy vol.14, pp.1, 2018, https://doi.org/10.1080/15548627.2017.1384887
  11. Corticosterone-Induced Lipogenesis Activation and Lipophagy Inhibition in Chicken Liver Are Alleviated by Maternal Betaine Supplementation vol.148, pp.3, 2018, https://doi.org/10.1093/jn/nxx073
  12. BAY 11-7085 induces glucocorticoid receptor activation and autophagy that collaborate with apoptosis to induce human synovial fibroblast cell death vol.7, pp.17, 2014, https://doi.org/10.18632/oncotarget.8042
  13. Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19 vol.22, pp.8, 2014, https://doi.org/10.3390/ijms22084067
  14. Calcium Signaling Regulates Autophagy and Apoptosis vol.10, pp.8, 2021, https://doi.org/10.3390/cells10082125