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 journalArticlepeer-review

5 Scopus citations


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
Issue number12
StatePublished - Dec 1 2018


  • 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


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