Cystic fibrosis CFTR

Robertson NH, Weston SL, Kelly SJ, Duxbury NJ, Pearce SR, Elsmore P, Webb MBT, Newton CR, Little S. Development and validation of a screening test for 12 common mutations of the cystic fibrosis CFTR gene. Eur Respir J 1998 12 477-482. 

Cystic fibrosis CFTR Misfolding/altered Hsp70 and calnexin interactions... 

The mechanism by which cholera toxin causes secretory diarrhea is through continuous stimulation of the CFTR-regulated CL channel (Figure 12-15). In cystic fibrosis, CFTR defects cause the abolition of intestinal chloride secretion without affecting the absorptive capacity. In homozygous CF patients, the disease is eventually lethal (discussed earlier). In cholera infections, however, CFTR is overactivated with fluid and electrolyte losses that lead to... 

Cystic fibrosis (CFTR gene) Inheritance autosomal recessive Location chromosome 7 (7q31) Mutation deletion of 3 bp at codonSOS accounts for 70% of mutations Huntington disease ... 

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cychc adenosine monophosphate (cAMP)-regulated chloride channel whose mutation can generate the hereditary disease cystic fibrosis. CFTR inhibition is a therapeutic potential approach to secretory diarrhea [23-25]. 3-[(3-Tiifluoromethyl)phenyl]-5-[(4-caiboxypheityl)methylene]-2-thioxo-4-thiazolidinone (CFTRjjj -172 Schemes... 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

The gene defective in cystic fibrosis codes for CFTR (cystic fibrosis transmembrane condnctance regulator), a membrane protein that pumps CP out of cells. If this CP pump is defective, CP ions remain in cells, which then take up water from the surrounding mucus by osmosis. The mucus thickens and accumulates in various organs, including the lungs, where its presence favors infections such as pneumonia. Left untreated, children with cystic fibrosis seldom survive past the age of 5 years. 

CFTR has a single-channel conductance of about 8 pS. It is present in the apical membranes of many epithelia. Its mutation leads to the potentially lethal disease cystic fibrosis. In addition to acting as a chloride channel, CFTR is also thought to regulate, e.g., the epithelial sodium channel ENaC, a molecularly unknown outwardly-rectifying chloride channel, and possibly also potassium channels and water channels. Some of these potential regulatory processes, however, are controversial. CFTR also acts as a receptor for bacteria. 

Disorders caused by misfolded mutant proteins that fail to pass the quality control system of the ER (e.g., mutations of the cystic fibrosis transmembrane regulator protein (CFTR) causing cystic fibrosis). The mutant proteins are retrotranslocated into the cytosol and finally subjected to proteolysis. In some... 

Cystic fibrosis Cystic fibrosis transmembrane conductance regulator (CFTR) Benzo(c)quinolizinium derivatives, VRT-325... 

Cystic fibrosis (MIM 219700) Mutations in the gene encoding the CFTR protein, a Cl" transporter... 

Figure 41-17. Diagram of the structure of the CFTR protein (not to scale). The protein contains twelve transmembrane segments (probably helical), two nucleotide-binding folds or domains (NBFl and NBF2), and one regulatory (R) domain. NBFl and NBF2 probably bind ATP and couple its hydrolysis to transport of Cl . Phe 508, the major locus of mutations in cystic fibrosis, is located in NBFl.

Cystic fibrosis (MIM 219700) CFTR(C - channel) Lungs, pancreas... 

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride (CF) channel characterised by chloride permeability and secretion, and also by the regulation of other epithelial ion channels (Eidelman et al, 2001). Mutations in the CFTR gene lead to an impaired or absent Cl conductance in the epithelial apical membrane, which leads to defective Cl secretion and absorption across the epithelium. Genistein (Illek et al, 1995 Weinreich et al, 1997) and other flavonoids (Illek and Fisher, 1998) have been shown, in different animal and tissue models, to activate wild-type CFTR and CFTR mutants by (Eidelman et al, 2001 Roomans, 2001 Suaud et al, 2002) ... 

O In CF, the cystic fibrosis transmembrane regulator (CFTR) chloride channel is dysfunctional and usually results in decreased chloride secretion and increased sodium absorption, leading to altered viscosity of fluid excreted by the exocrine glands and mucosal obstruction. 

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