Misassembled mutant ΔF508 CFTR in the distal secretory pathway alters cellular lipid trafficking
نویسندگان
چکیده
منابع مشابه
Decreasing Poly(ADP-Ribose) Polymerase Activity Restores ΔF508 CFTR Trafficking
Most cystic fibrosis is caused by mutations in CFTR that prevent its trafficking from the ER to the plasma membrane and is associated with exaggerated inflammation, altered metabolism, and diminished responses to oxidative stress. PARP-1 is activated by oxidative stress and causes energy depletion and cell dysfunction. Inhibition of this enzyme protects against excessive inflammation and recent...
متن کاملRescue of ΔF508-CFTR Trafficking via a GRASP-Dependent Unconventional Secretion Pathway
The most prevalent disease-causing mutation of CFTR is the deletion of Phe508 (ΔF508), which leads to defects in conventional Golgi-mediated exocytosis and cell surface expression. We report that ΔF508-CFTR surface expression can be rescued in vitro and in vivo by directing it to an unconventional GRASP-dependent secretion pathway. An integrated molecular and physiological analysis indicates th...
متن کاملDiminished Self-Chaperoning Activity of the ΔF508 Mutant of CFTR Results in Protein Misfolding
The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and c...
متن کاملPotential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides that Restore Trafficking and Activity of ΔF508-CFTR.
Cystic fibrosis (CF) is a loss-of-function disease caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, a chloride ion channel that localizes to the apical plasma membrane of epithelial cells. The most common form of the disease results from the deletion of phenylalanine-508 (ΔF508), leading to the accumulation of CFTR in the endoplasmic reticulum with a concomitant...
متن کاملAn LQT mutant minK alters KvLQT1 trafficking.
Cardiac I(Ks), the slowly activated delayed-rectifier K(+) current, is produced by the protein complex composed of alpha- and beta-subunits: KvLQT1 and minK. Mutations of genes encoding KvLQT1 and minK are responsible for the hereditary long QT syndrome (loci LQT1 and LQT5, respectively). MinK-L51H fails to traffic to the cell surface, thereby failing to produce effective I(Ks). We examined the...
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ژورنال
عنوان ژورنال: Journal of Cell Science
سال: 2007
ISSN: 1477-9137,0021-9533
DOI: 10.1242/jcs.03350