Cystic fibrosis (CF) is caused by mutations in a gene that encodes a protein known as CFTR. More than 1000 different disease-causing mutations in CFTR have been identified, and although the overall effect of each mutation is to decrease CFTR expression at the cell surface, it is not known for every one of these mutations what the molecular defect is that causes the decreased cell surface expression of CFTR.
Now, researchers from the University of North Carolina at Chapel Hill have shown that one specific mutation in CFTR (the S13F mutation) prevents CFTR from interacting with proteins known as filamins, which are essential for maintaining CFTR at the cell membrane.
In the study, which appears online on January 18 in advance of publication in the February print issue of the Journal of Clinical Investigation, Sharon Milgram and colleagues show that when expressed in cultured human cell lines, S13F mutant CFTR is not maintained at the cell surface and is degraded more rapidly than normal CFTR. Furthermore, normal CFTR interacts with proteins known as filamins, whereas S13F mutant CFTR does not. Having identified that filamins are important for maintaining cell surface expression of CFTR it will be necessary to determine how filamins interact with other proteins involved in maintaining CFTR at the cells surface. This might provide insight into how further CF-causing mutations in CFTR cause disease.