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http://dx.doi.org/10.14348/molcells.2014.2384

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)
Publication Information
Molecules and Cells / v.37, no.3, 2014 , pp. 257-263 More about this Journal
Abstract
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.
Keywords
autophagy; glucocorticoid (cortisol); protein degradation; TRPV1;
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1 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.   DOI   ScienceOn
2 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.   DOI   ScienceOn
3 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.   DOI   ScienceOn
4 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.   DOI   ScienceOn
5 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.   DOI   ScienceOn
6 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.   DOI   ScienceOn
7 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.   DOI   ScienceOn
8 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.   DOI   ScienceOn
9 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.
10 Ross, R.A. (2003). Anandamide and vanilloid TRPV1 receptors. Br. J. Pharmacol. 140, 790-801.   DOI   ScienceOn
11 Mizushima, N., and Komatsu, M. (2011). Autophagy: renovation of cells and tissues. Cell 147, 728-741.   DOI   ScienceOn
12 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.   DOI   ScienceOn
13 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.   DOI   ScienceOn
14 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.   DOI   ScienceOn
15 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)).
16 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.
17 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.   DOI
18 Wallace, A.D., and Cidlowski, J.A. (2001). Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids. J. Biol. Chem. 276, 42714-42721.   DOI   ScienceOn
19 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.   DOI
20 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.   DOI
21 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.   DOI   ScienceOn
22 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.   DOI   ScienceOn
23 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.   DOI   ScienceOn
24 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.   DOI   ScienceOn
25 Clapham, D.E. (2003). TRP channels as cellular sensors. Nature 426, 517-524.   DOI   ScienceOn
26 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.   DOI
27 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.   DOI   ScienceOn
28 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.   DOI   ScienceOn
29 Goswami, C., and Hucho, T. (2007). TRPV1 expression-dependent initiation and regulation of filopodia. J. Neurochem. 103, 1319-1333.   DOI   ScienceOn
30 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.   DOI   ScienceOn
31 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.   DOI   ScienceOn
32 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.   DOI
33 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.   DOI
34 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.   DOI   ScienceOn