ABCMdb

PMID: 9922379

Schwiebert EM, Benos DJ, Egan ME, Stutts MJ, Guggino WB
CFTR is a conductance regulator as well as a chloride channel.
Physiol Rev. 1999 Jan;79(1 Suppl):S145-66., [PubMed]

Sentences

No. Mutations Sentence Comment

75 ABCC7 p.Gly551Asp Severe mutations, such as G551D or DF508, are present in CF patients that are pancreatic insufficient and havechannels that are regulated by ATP via ATP receptors M0000 P18-8/ 9j0e$$ja03 01-13-99 15:02:43 prsa APS-Phys Rev more severe lung disease. Login to comment 92 ABCC7 p.Met265Val In sharp contrast, a similar truncation to amino acid 259 Taken together, these preliminary results utilizing truncations of the CFTR cDNA from the NH2 and COOHbut with methionine-265 altered to a valine (M265V) failed to function as a cAMP-stimulated Cl0 channel in termini suggest that the domains critical for Cl0 channel function and ORCC regulatory coupling are distinct. Login to comment 94 ABCC7 p.Met265Val However, despite this lack of Cl0 channel activity, M265V conferred cAMP regulation function could be eliminated with the other intact, and vice versa. Login to comment 101 ABCC7 p.Met265Val Similar to the results with M265V, insertion of ''dual`` NBD1 in bilayers (7) and mammalian cells (34) (see also below). Login to comment 102 ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro Nevertheless, cAMP-stimulated ATP release andarginine mutations (R334W with R347P) into CFTR eliminated Cl0 channel activity but conferred cAMP ORCC regulatory interaction are interconnected in CF airway epithelial cells. Login to comment 108 ABCC7 p.Ala455Glu A''half molecule`` of CFTR (TNR-CFTR) in which amino acids 836 through 1480 were eliminated (TMD-1, NBD1, mild mutation within NBD1, A455E, caused a small reduction in Cl0 channel function but did not affect cAMP stim-and R domains of CFTR intact) functioned in oocytes as a 9-pS single Cl0 channel similar to wild-type CFTR. Login to comment 110 ABCC7 p.Gly551Asp In contrast, G551D, a common and se- M0000 P18-8/ 9j0e$$ja03 01-13-99 15:02:43 prsa APS-Phys Rev FIG. 3. Login to comment 155 ABCC7 p.Gly551Asp Remarkably, the intimate regulatory relationship between these two pro-and the nonconducting G551D CFTR were incorporated simultaneously into the planar lipid bilayer. Login to comment 162 ABCC7 p.Gly551Asp Thus, on the basis of the findings with dysfunctional G551D-CFTRG551D-CFTR (72). Login to comment 219 ABCC7 p.Met265Val Wild-type and D259- M265V-CFTR promote cAMP-stimulated ATP release from oocytes, whereas TMD-1 CFTR fails to promote cAMP-stimulated ATP release. Login to comment 229 ABCC7 p.Gly551Asp For hypothesis A to occur based on anconstituted CFTR from bovine tracheal epithelia and the overview of data in literature, appropriate cofactors or regulatory pro-nonconducting G551D-CFTR from transformed L cells, teins must be expressed in concert with CFTR. Login to comment 288 ABCC7 p.Gly551Asp Indeed, insertion of the G551D mutation into NBD1 disrupted func- concert, such as the sweat duct epithelium. Login to comment 416 ABCC7 p.Lys593* Cystic fibrosis transmembrane con- when a truncated CFTR construct that contains a functioning NBF1 (K593X) was expressed with ROMK2, Ç50%ductance regulator could be coupled with either ROMK1 or ROMK2 in the cell membrane, providing a missing of K/ current was glibenclamide sensitive, demonstrating a significant but not complete inhibition (130). Login to comment 417 ABCC7 p.Gly551Asp The G551D/domain to the cloned channels, thus restoring sulfonylurea sensitivity. Login to comment 418 ABCC7 p.Lys593* Alternatively, the mechanism that con- ROMK2 and K593X/ROMK2 data suggest that the interaction between CFTR and ROMK2 may require a functionaltrols the CFTR-ROMK2 interaction could involve a regulatory protein or a cytoskeletal element. Login to comment 441 ABCC7 p.Gly551Asp In two-microelectrode voltage-clamp studies, when ROMK2 was expressed with the CFTR mutant G551D, by associated genetic factors such as modifier gene loci. Login to comment