Endocytobiology III (Annals of the New York Academy of by John J. & Jerome F. Fredrick (editors) LEE
By John J. & Jerome F. Fredrick (editors) LEE
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Extra resources for Endocytobiology III (Annals of the New York Academy of Sciences, 503)
3). IV. Mucociliary Clearance Inhaled particulates and pathogens routinely reach the lower airways, but are typically trapped within the mucus layer and transported out of the lung via mucus clearance mechanisms without the need to mount a potentially deleterious inflammatory response. Mucus clearance, therefore, is widely considered to be the primary innate airway defense mechanism (3). Perhaps the clearest example of the direct relationship between defective MCC and disease is provided by patients with primary ciliary dyskinesia (PCD), who have defective or absent ciliary activity.
Denning GM, Anderson MP, Amara JF, et al. Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature 1992; 358(6389):761–764. 28. Dalemans W, Barbry P, Champigny G, et al. Altered chloride channel kinetics associated with the deltaF508 cystic fibrosis mutation. Nature 1991; 354:526–528. 29. Randak C, Welsh MJ. An intrinsic adenylate kinase activity regulates gating of the ABC transporter CFTR. Cell 2003; 115(7):837–850. 10 Suaud and Rubenstein 30. Logan J, Hiestand D, Daram P, et al.
Phosphorylation of CFTR is necessary for CFTR activation (28), and CFTR channels are deactivated upon dephosphorylation carried out by protein phosphatases (34,35). The amino and carboxyl terminal regions have specific amino acid residues that allow CFTR to bind to intracellular proteins (36). For example, the carboxyl terminus interacts with the scaffolding protein NHERF-1 (37), which modulates channel gating (38) and enables CFTR to interact with other proteins (39). In addition to CFTR channel activity regulation by nucleotide binding, phosphorylation, and protein interactions, the amount of CFTR in the plasma membrane is also regulated by its trafficking and recycling in and out of the apical membrane of epithelial cells (40,41).