Cross-linking of ΔF508-CFTR promotes its trafficking to the plasma membrane.
CFTR is a cAMP-activated chloride channel responsible for agonist stimulated chloride and fluid transport across epithelial surfaces.(1) Mutations in the CFTR gene lead to cystic fibrosis (CF) which affects the function of secretory organs like the intestine, the pancreas, the airways and the sweat glands. Most of the morbidity and mortality in CF has been linked to a decrease in airway function.(2) The ΔF508 mutation is the most common CF-related mutation in the Caucasian population and represents 90% of CF alleles. Homozygote carriers of this mutation present with a severe CF phenotype.(3) The ΔF508 mutation causes misfolding of the nascent CFTR polypeptide, which leads to inefficient export from the endoplasmic reticulum (ER) and rapid degradation by the proteasome.
Bernard
Karen
K
Department of Physiology and Biophysics and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Kirk
Kevin L
KL
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D055503:Protein Multimerization; D021381:Protein Transport; D013388:Succinimides / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
C505032:CFTR protein, human; D003432:Cross-Linking Reagents; D013388:Succinimides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin; C019358:disuccinimidyl suberate