FKBP8 enhances protein stability of the CLC-1 chloride channel at the plasma membrane

Yi Jheng Peng, Yi Ching Lee, Ssu Ju Fu, Yun Chia Chien, Yi Fan Liao, Tsung-Yu Chen, Chung Jiuan Jeng, Chih Yung Tang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Mutations in the skeletal muscle-specific CLC-1 chloride channel are associated with the human hereditary disease myotonia congenita. The molecular pathophysiology underlying some of the disease-causing mutations can be ascribed to defective human CLC-1 protein biosynthesis. CLC-1 protein folding is assisted by several molecular chaperones and co-chaperones, including FK506-binding protein 8 (FKBP8). FKBP8 is generally considered an endoplasmic reticulum-and mitochondrion-resident membrane protein, but is not thought to contribute to protein quality control at the cell surface. Herein, we aim to test the hypothesis that FKBP8 may regulate CLC-1 protein at the plasma membrane. Surface biotinylation and subcellular fractionation analyses reveal that a portion of FKBP8 is present at the plasma membrane, and that co-expression with CLC-1 enhances surface localization of FKBP8. Immunoblotting analyses of plasma membrane proteins purified from skeletal muscle further confirm surface localization of FKBP8. Importantly, FKBP8 promotes CLC-1 protein stability at the plasma membrane. Together, our data underscore the importance of FKBP8 in the peripheral quality control of CLC-1 channel.

Original languageEnglish (US)
Article number3783
JournalInternational Journal of Molecular Sciences
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Tacrolimus Binding Proteins
Chloride Channels
Protein Stability
Cell membranes
chlorides
Cell Membrane
membranes
proteins
Proteins
Quality Control
Quality control
Muscle
Membrane Proteins
Skeletal Muscle
Myotonia Congenita
Biotinylation
skeletal muscle
Protein folding
Mutation
Inborn Genetic Diseases

Keywords

  • Ion channels
  • Membrane proteins
  • Molecular chaperones
  • Protein stability
  • Skeletal muscle
  • Trafficking

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

FKBP8 enhances protein stability of the CLC-1 chloride channel at the plasma membrane. / Peng, Yi Jheng; Lee, Yi Ching; Fu, Ssu Ju; Chien, Yun Chia; Liao, Yi Fan; Chen, Tsung-Yu; Jeng, Chung Jiuan; Tang, Chih Yung.

In: International Journal of Molecular Sciences, Vol. 19, No. 12, 3783, 01.12.2018.

Research output: Contribution to journalArticle

Peng, Yi Jheng ; Lee, Yi Ching ; Fu, Ssu Ju ; Chien, Yun Chia ; Liao, Yi Fan ; Chen, Tsung-Yu ; Jeng, Chung Jiuan ; Tang, Chih Yung. / FKBP8 enhances protein stability of the CLC-1 chloride channel at the plasma membrane. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 12.
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