CFTR: more than just a chloride channel.
This review examines the cystic fibrosis transmembrane conductance regulator (CFTR) protein. After summarizing the ion channels regulated by CFTR, the review focuses on the functions of CFTR that do not relate directly to a disease mechanism based on a channelopathy. The key concept is that newly synthesized CFTR has to enter lipid vesicles which bud from the endoplasmic reticulum. This is abnormally low in DeltaF508 CFTR. Normal wild type vesicular CFTR enters a recycling pool of lipid vesicles which transiently dock with the apical membrane only for CFTR to be retrieved shortly after into a sub-apical recycling compartment. This retrieval is abnormally fast in DeltaF508 CFTR. The review discusses the relationship between this process and the difficult topic of fat metabolism and then explores the possible links between abnormal fatty acid turnover and inflammatory cascades that are abnormal in cystic fibrosis. Finally the review concentrates on the emerging functions of a protein kinase (AMP-activated kinase) which is bound near the C terminus of the CFTR protein whose functions could intergrate some of the abnormalities in lipid metabolism that result from mislocalization of CFTR in clinical disease.
Mehta
Anil
A
Division of Maternal and Child Health Sciences, Ninewells Hospital Medical School, Dundee, Scotland, UK. a.mehta@dundee.ac.uk
D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D017136:Ion Transport / Q000502:physiology; D008168:Lung / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator