TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease

Chansik Hong, Seo Hwa Choi, Misun Kwak, Byeongseok Jeong, Juyeon Ko, Hyung Joon Park, Seok Choi, Jae Yeoul Jun, Insuk So

Research output: Contribution to journalArticle

Abstract

Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16‑carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization. Especially, neurodevelopment is regulated by balancing the level of synaptic protein palmitoylation/depalmitoylation. Recently, we revealed the pathological role of the transient receptor potential canonical type 5 (TRPC5) channel in striatal neuronal loss during Huntington's disease (HD), which is abnormally activated by oxidative stress. Here, we report a mechanism of TRPC5 palmitoylation at a conserved cysteine residue, that is critical for intrinsic channel activity. Furthermore, we identified the therapeutic effect of TRPC5 depalmitoylation by enhancing the TRPC5 membrane instability on HD striatal cells in order to lower TRPC5 toxicity. Collectively, these findings suggest that controlling S-palmitoylation of the TRPC5 channel as a potential risk factor can modulate TRPC5 channel expression and activity, providing new insights into a therapeutic strategy for neurodegenerative diseases.

Original languageEnglish
Article number118620
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1867
Issue number2
DOIs
StatePublished - Feb 2020

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Lipoylation
Corpus Striatum
Huntington Disease
Oxidative Stress
Neurons
Ion Channels
Membranes
Acylation
Palmitates
Protein S
Therapeutic Uses
Post Translational Protein Processing
Life Cycle Stages
Neurodegenerative Diseases
Cysteine
Fatty Acids
Lipids
Proteins

Keywords

  • Depalmitoylation
  • HD
  • Palmitoylation
  • TRPC
  • Trafficking

Cite this

Hong, Chansik ; Choi, Seo Hwa ; Kwak, Misun ; Jeong, Byeongseok ; Ko, Juyeon ; Park, Hyung Joon ; Choi, Seok ; Jun, Jae Yeoul ; So, Insuk. / TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2020 ; Vol. 1867, No. 2.
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TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease. / Hong, Chansik; Choi, Seo Hwa; Kwak, Misun; Jeong, Byeongseok; Ko, Juyeon; Park, Hyung Joon; Choi, Seok; Jun, Jae Yeoul; So, Insuk.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1867, No. 2, 118620, 02.2020.

Research output: Contribution to journalArticle

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AU - Hong, Chansik

AU - Choi, Seo Hwa

AU - Kwak, Misun

AU - Jeong, Byeongseok

AU - Ko, Juyeon

AU - Park, Hyung Joon

AU - Choi, Seok

AU - Jun, Jae Yeoul

AU - So, Insuk

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