ABCMdb

PMID: 8557666

Sato S, Ward CL, Krouse ME, Wine JJ, Kopito RR
Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation.
J Biol Chem. 1996 Jan 12;271(2):635-8., [PubMed]

Sentences

No. Mutations Sentence Comment

91 ABCC7 p.Ser1251Ala ABCC7 p.Asp572Ala Cells expressing the missense mutants D572A and S1251A and a mutant harboring a deletion of exon 13 (⌬EX13) were pulse-labeled with [35 S]Met and chased for 5 h in the presence or absence of glycerol (Fig. 3A). Login to comment 93 ABCC7 p.Ser1251Ala ABCC7 p.Ser1251Ala ABCC7 p.Asp572Ala ABCC7 p.Asp572Ala Thus, some mutations in all three major cytoplasmic domains of CFTR, including the first and second nucleotide binding domains (D572A and S1251A, respectively) as well as the "R" domain, can lead to a glycerol-insensitive ER retention phenotype, suggesting that glycerol treatment does not induce a general suppression of ER retention mechanisms. Login to comment 95 ABCC7 p.Lys464Ala ABCC7 p.Ser1251Ala ABCC7 p.Asp572Ala ABCC7 p.Lys464Arg Processing of mutants K464R and K464A was inefficient by comparison with wild type and was enhanced by incubation in the presence of 10% glycerol, even after accounting for the unequal label present in the immature precursor in the presence of glycerol (Fig. 3B). Login to comment 96 ABCC7 p.Lys464Trp By contrast, no maturation was detectable for the mutant K464W in the presence or absence of glycerol. Login to comment 97 ABCC7 p.Lys464Ala ABCC7 p.Lys464Arg Processing of mutants K464R and K464A was inefficient by comparison with wild type and was enhanced by incubation in the presence of 10% glycerol, even after accounting for the unequal label present in the immature precursor in the presence of glycerol (Fig. 3B). Login to comment 98 ABCC7 p.Lys464Trp By contrast, no maturation was detectable for the mutant K464W in the presence or absence of glycerol. Login to comment 108 ABCC7 p.Asp572Ala HEK cells expressing D572A, ⌬EX13, and S1251 (A) or various substitutions at Lys464 (B) were pulse-labeled (p) for 15 min and chased for 5 h (c) in the presence or the absence of glycerol. Login to comment 110 ABCC7 p.Asp572Ala HEK cells expressing D572A, DEX13, and S1251 (A) or various substitutions at Lys464 (B) were pulse-labeled (p) for 15 min and chased for 5 h (c) in the presence or the absence of glycerol. Login to comment 122 ABCC7 p.Lys464Ala ABCC7 p.Lys464Arg Interestingly, we observe a strong correlation between the temperature sensitivity of CFTR mutations like ⌬F508, K464R, and K464A (data not shown) and their ability to be remediated by glycerol. Login to comment 124 ABCC7 p.Lys464Ala ABCC7 p.Lys464Arg Interestingly, we observe a strong correlation between the temperature sensitivity of CFTR mutations like DF508, K464R, and K464A (data not shown) and their ability to be remediated by glycerol. Login to comment