Low temperature induces the delivery of mature and immature CFTR to the plasma membrane.
Deletion of phenylalanine 508 (DeltaF508) is the most prevalent disease-causing mutation resulting in retention of the immature CFTR in the endoplasmic reticulum. The most common strategy to induce the delivery of DeltaF508-CFTR to the surface of cells is by reducing the incubation temperature ( approximately 28 degrees C). Cell surface biotinylation of HEK293T cells grown at 37 degrees C for 48h, confirmed the presence of mature wild-type CFTR, but not DeltaF508-CFTR at the cell surface. On the other hand, cells incubated at 28 degrees C for 16h showed both mature and immature DeltaF508-CFTR at their surface. The trafficking of immature DeltaF508-CFTR, but not mature DeltaF508-CFTR, to the cell surface occurred at low temperature even upon addition of BFA, suggesting the involvement of a Golgi-independent pathway. These results suggest that low temperature induces the appearance of a mix population of mature and immature CFTR molecules at the plasma membrane through distinct pathways.
Rennolds
Jessica
J
Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210-1252, USA.
Boyaka
Prosper N
PN
Bellis
Susan L
SL
Cormet-Boyaka
Estelle
E
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003080:Cold Temperature; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D021381:Protein Transport
D019012:Integrin beta1; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator