Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β

Yi Jheng Peng, Jing Jia Huang, Hao Han Wu, Hsin Ying Hsieh, Chia Ying Wu, Shu Ching Chen, Tsung-Yu Chen, Chih Yung Tang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation.

Original languageEnglish (US)
Article number32444
JournalScientific Reports
Volume6
DOIs
StatePublished - Sep 1 2016

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Tacrolimus Binding Proteins
HSP90 Heat-Shock Proteins
Chloride Channels
Cullin Proteins
Quality Control
tanespimycin
Proteolysis
Proteins
Myotonia Congenita
Molecular Chaperones
Protein Stability
Protein Folding
Muscular Diseases
Ligases
Ubiquitin
CLC-1 channel
Adenosine Triphosphatases
Skeletal Muscle
Mutation

ASJC Scopus subject areas

  • General

Cite this

Peng, Y. J., Huang, J. J., Wu, H. H., Hsieh, H. Y., Wu, C. Y., Chen, S. C., ... Tang, C. Y. (2016). Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β. Scientific Reports, 6, [32444]. https://doi.org/10.1038/srep32444

Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β. / Peng, Yi Jheng; Huang, Jing Jia; Wu, Hao Han; Hsieh, Hsin Ying; Wu, Chia Ying; Chen, Shu Ching; Chen, Tsung-Yu; Tang, Chih Yung.

In: Scientific Reports, Vol. 6, 32444, 01.09.2016.

Research output: Contribution to journalArticle

Peng, YJ, Huang, JJ, Wu, HH, Hsieh, HY, Wu, CY, Chen, SC, Chen, T-Y & Tang, CY 2016, 'Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β', Scientific Reports, vol. 6, 32444. https://doi.org/10.1038/srep32444
Peng YJ, Huang JJ, Wu HH, Hsieh HY, Wu CY, Chen SC et al. Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β. Scientific Reports. 2016 Sep 1;6. 32444. https://doi.org/10.1038/srep32444
Peng, Yi Jheng ; Huang, Jing Jia ; Wu, Hao Han ; Hsieh, Hsin Ying ; Wu, Chia Ying ; Chen, Shu Ching ; Chen, Tsung-Yu ; Tang, Chih Yung. / Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β. In: Scientific Reports. 2016 ; Vol. 6.
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