ABCMdb

PMID: 7541313

Schwiebert EM, Egan ME, Hwang TH, Fulmer SB, Allen SS, Cutting GR, Guggino WB
CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP.
Cell. 1995 Jun 30;81(7):1063-73., [PubMed]

Sentences

No. Mutations Sentence Comment

126 ABCC7 p.Ala455Glu (<3)Bar graphillustratingpercentcAMP-stimu- latedgenerationofglucose-6--32PinIB3-1cells, IB3-1 cellsstablytransfectedwithan AAVin- vertedterminalrepeatpromotor-drivenwild- typeCFTRviralvector(Eganetal, 1992;Flotte et al., 1993;Schwiebertet al., 1994a),or IB3-1cellstransientlytransfectedwithwild-typeor mutantCFTR(A455E-CFTRandG551D-CFTR).Data areexpressedtopercentchangeversuscontrol.Dataareexpressedasmean_ SEM.Numberinparenthesesisnumberofexperimentsperformed. Login to comment 130 ABCC7 p.Ala455Glu (<3)Bar graphillustratingpercentcAMP-stimu- latedgenerationofglucose-6--32P inIB3-1cells, IB3-1 cellsstablytransfectedwithan AAVin- vertedterminalrepeatpromotor-drivenwild- typeCFTRviralvector(Eganetal, 1992;Flotte et al., 1993;Schwiebertet al., 1994a),or IB3-1cellstransientlytransfectedwithwild-typeor mutantCFTR(A455E-CFTRandG551D-CFTR).Data areexpressedtopercentchangeversuscontrol.Dataareexpressedasmean_ SEM.Numberinparenthesesisnumberofexperimentsperformed. Login to comment 145 ABCC7 p.Ala455Glu Interestingly, two mutations located in the first nucleotide-binding domain of CFTR, A455E-CFTR, a mutation associated with mild CF pulmonary disease, and G551 D-CFTR, a mutation associated with severe CF lung disease, had different effects on the ability of CFTR to trigger ATP release. Login to comment 146 ABCC7 p.Ala455Glu IB3-1 CF cells transientlytransfected with A455E reestablished cAMP-stimulated ATP release, although the magnitude was not as large compared with wild-type CFTR (Figure 4C). Login to comment 147 ABCC7 p.Gly551Asp In sharp contrast, G551D failed to complement cAMP-stimulated ATP release in IB3-1 CF cells (Figure 4C). Login to comment 149 ABCC7 p.Ala455Glu Interestingly, two mutations located in the first nucleotide-binding domain of CFTR, A455E-CFTR, a mutation associated with mild CF pulmonary disease, and G551 D-CFTR, a mutation associated with severe CF lung disease, had different effects on the ability of CFTR to trigger ATP release. Login to comment 150 ABCC7 p.Ala455Glu IB3-1 CF cells transientlytransfected with A455E reestablished cAMP-stimulated ATP release, although the magnitude was not as large compared with wild-type CFTR (Figure 4C). Login to comment 151 ABCC7 p.Gly551Asp In sharp contrast, G551D failed to complement cAMP-stimulated ATP release in IB3-1 CF cells (Figure 4C). Login to comment 155 ABCC7 p.Gly551Asp occur in CF cells that contain CFTR bearing either AF508 (mutation in parental IB3-1 cells) or G551D mutations. Login to comment 159 ABCC7 p.Gly551Asp occur in CF cells that contain CFTR bearing either AF508 (mutation in parental IB3-1 cells) or G551D mutations. Login to comment 209 ABCC7 p.Gly551Asp ABCC7 p.Ala455Glu Further support for this hypothesis is that CFTR bearing an A455E mutation, which is associated with mild CF lung disease, can induce ATP release, whereas CFTR bearing a more severe G551D mutation fails to trigger ATP release. Login to comment 210 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu In a separate study, it was shown that both of the mutant forms of CFTR, A455E and G551D, could function as cAMP-activated CI- channels, although the function of G551D was much reduced compared with that of wild-type or A455E CFTR (Fulmer et al., 1995). Login to comment 211 ABCC7 p.Gly551Asp ABCC7 p.Ala455Glu Importantly, only A455E and not G551D could correct cAMP regulation of ORCCs in IB3-1 CF cells (Fulmer et al., 1995). Login to comment 213 ABCC7 p.Gly551Asp ABCC7 p.Ala455Glu Further support for this hypothesis is that CFTR bearing an A455E mutation, which is associated with mild CF lung disease, can induce ATP release, whereas CFTR bearing a more severe G551D mutation fails to trigger ATP release. Login to comment 214 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu In a separate study, it was shown that both of the mutant forms of CFTR, A455E and G551D, could function as cAMP-activated CI-channels, although the function of G551D was much reduced compared with that of wild-type or A455E CFTR (Fulmer et al., 1995). Login to comment 215 ABCC7 p.Gly551Asp ABCC7 p.Ala455Glu Importantly, only A455E and not G551D could correct cAMP regulation of ORCCs in IB3-1 CF cells (Fulmer et al., 1995). Login to comment 227 ABCC7 p.Trp1282* IB3-1 cells are a CF human bronchial epithelial cell line derived from a CF patient compound heterozygous for the AF508 mutation (~F508/W1282X) (Zeitlin et al., 1991; Egan et al., 1992). Login to comment 231 ABCC7 p.Trp1282* IB3-1 cells are a CF human bronchial epithelial cell line derived from a CF patient compound heterozygous for the AF508 mutation (~F508/W1282X) (Zeitlin et al., 1991; Egan et al., 1992). Login to comment