Peng Y.-J.Lee Y.-C.Fu S.-J.Chien Y.-C.Liao Y.-F.Chen T.-Y.Jeng C.-J.CHIH-YUNG TANG2020-06-302020-06-3020181661-6596https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057553848&doi=10.3390%2fijms19123783&partnerID=40&md5=671b71776affec54f62c1d1592fcafd2https://scholars.lib.ntu.edu.tw/handle/123456789/506982Mutations 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. ? 2018 by the authors. Licensee MDPI, Basel, Switzerland.Ion channels; Membrane proteins; Molecular chaperones; Protein stability; Skeletal muscle; Trafficking[SDGs]SDG3calnexin; chaperone; fk 506 binding protein; glucose regulated protein 78; glutathione transferase; glyceraldehyde 3 phosphate dehydrogenase; heat shock cognate protein 70; heat shock protein; heat shock protein 90; outer membrane protein; streptavidin; voltage gated chloride channel; chloride channel; CLC-1 channel; fk 506 binding protein; FKBP8 protein, human; membrane protein; Article; biotinylation; cell culture; cell fractionation; cell membrane; cell migration; cell surface; chemoluminescence; controlled study; cytosol; densitometry; DNA transfection; endoplasmic reticulum; erythrocyte sedimentation rate; gene expression; gene mutation; gene overexpression; genetic disorder; Golgi complex; HEK293T cell line; human; human cell; immunoblotting; immunofluorescence; immunoprecipitation; mitochondrion; molecular pathology; oncogene myc; protein expression; protein localization; protein purification; protein stability; protein synthesis; quality control; sarcoplasmic reticulum; skeletal muscle; Thomsen disease; vastus lateralis muscle; cell membrane; HEK293 cell line; metabolism; protein stability; Cell Membrane; Chloride Channels; Golgi Apparatus; HEK293 Cells; Humans; Membrane Proteins; Muscle, Skeletal; Protein Stability; Tacrolimus Binding Proteinsjournal article10.3390/ijms19123783304873932-s2.0-85057553848