Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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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)
  • Received : 2013.12.23
  • Accepted : 2014.02.17
  • Published : 2014.03.31
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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.

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