Cystic fibrosis transmembrane

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. 

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... 

In Cystic fibrosis a point mutation of the cystic fibrosis transmembrane regulator (CTFR) prevents transport of this molecule to the cell surface. Instead this otherwise functional molecule is degraded by the ERAD-ubiquitin proteasome pathway. 

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. 

Cystic fibrosis transmembrane conductance exporter family... 

The 12-transmembrane-spanning domain topology of the adenylyl cyclase enzymes is similar to that found in the ABC family of transporters (see Ch. 5), which includes the cystic fibrosis transmembrane rectifier and the P-glyco-protein. However, there is currently no convincing evidence of a transporter or channel function for mammalian adenylyl cyclases. The structural similarity may indicate that these functionally divergent protein families are derived in an evolutionary sense from related proteins. 

A novel class of activators for chloride conductance in the cystic fibrosis transmembrane conductance regulator protein has been identified. These 3-(2-benzy-loxyphenyl)isoxazoles and 3-(2-benzyloxyphenyl)isoxazolines have been synthesized employing the 1,3-dipolar cycloaddition of nitrile oxides with various alkene and alkyne dipolarophiles (490). 

CFTR Cystic fibrosis transmembrane conductance regulator... 

Wagner, J. A., T. V. McDonald, P. T. Nghiem, A. W. Lowe, H. Schulman, D. C. Gruenert, L. Stryer, and P. Gardner. 1992. Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance regulator inhibit cAMP-activated but not calcium-activated chloride currents. Proc Natl Acad Sci USA 89(15) 6785-9. 

CF is caused by the absence of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein is required for the transport of chloride ions across cell membranes. On the molecular level, there is a mutation in the gene that encodes for CFTR. As a result, CFTR cannot be processed properly by the cell and is unable to reach the exocrine glands to assume its transport function. 

Cheung M, Akabas MH. 1996. Identification of the cystic fibrosis transmembrane conductance regulator channellining residues in and flanking the M6 membrane-spanning segment. Biophys J 70 2688-2695. 

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