title: Functional analysis of F508del CFTR in native human colon.
abstract: The major cystic fibrosis mutation F508del has been classified by experiments in animal and cell culture models as a temperature-sensitive mutant defective in protein folding, processing and trafficking, but literature data on F508del CFTR maturation and function in human tissue are inconsistent. In the present study the molecular pathology of F508del CFTR was characterized in freshly excised rectal mucosa by bioelectric measurement of the basic defect and CFTR protein analysis by metabolic labelling or immunoblot. The majority of investigated F508del homozygous subjects expressed low amounts of complex-glycosylated mature F508del CFTR and low residual F508del CFTR-mediated chloride secretory activity in the rectal mucosa. The finding that some F508del CFTR escapes the ER quality control in vivo substantiates the hope that the defective processing and trafficking of F508del CFTR can be corrected by pharmacological agents.
authors.affiliation: Klinische Forschergruppe, OE 6710, Medizinische Hochschule Hannover, Hannover, Germany. barneveld.andrea.va@nk-hannover.de
authors.forename: Andrea
authors.initials: A
authors.lastname: van Barneveld
authors.forename: Frauke
authors.initials: F
authors.lastname: Stanke
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tamm
authors.forename: Benny
authors.initials: B
authors.lastname: Siebert
authors.forename: Gudrun
authors.initials: G
authors.lastname: Brandes
authors.forename: Nico
authors.initials: N
authors.lastname: Derichs
authors.forename: Manfred
authors.initials: M
authors.lastname: Ballmann
authors.forename: Sibylle
authors.initials: S
authors.lastname: Junge
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006031:Glycosylation; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D017136:Ion Transport / Q000187:drug effects; D008168:Lung / Q000378:metabolism / Q000473:pathology; D050505:Mutant Proteins / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D002712:Chlorides; D050505:Mutant Proteins; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000242:Cyclic AMP