Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland.
Misprocessing and mislocalization of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) has been described for the major CF-causing mutation (delta F508) in heterologous expression systems in vitro. We have generated monoclonal antibodies (mAbs) to CFTR with the aim of localizing the protein and its CF variants in vivo. Of the tissues where CFTR was observed, only the sweat gland is readily available and does not undergo secondary changes due to CF disease pathology. Sweat ducts from CF patients homozygous for delta F508 did not show the typical apical membrane staining seen in control biopsies. This demonstrates that the biosynthetic arrest and intracellular retention of delta F508 CFTR initially observed in vitro does occur in vivo and emphasizes the need to focus efforts on understanding the mislocalization.
Kartner
N
N
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Augustinas
O
O
Jensen
T J
TJ
Naismith
A L
AL
Riordan
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014644:Genetic Variation; D006801:Humans; D007422:Intestines / Q000502:physiology; D007473:Ion Channels / Q000235:genetics*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010179:Pancreas / Q000502:physiology; D011994:Recombinant Proteins / Q000032:analysis; D012016:Reference Values; D012143:Respiratory Physiological Phenomena; D015183:Restriction Mapping; D012377:Rodentia; D012469:Salivary Glands / Q000502:physiology; D012867:Skin / Q000503:physiopathology; D012879:Skin Physiological Phenomena; D013545:Sweat Glands / Q000502:physiology / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; C505032:CFTR protein, human; D007473:Ion Channels; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator