Molecular motors and apical CFTR traffic in epithelia

Abstract

Intracellular protein traffic plays an important role in the regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channels. Microtubule and actin-based motor proteins direct CFTR movement along trafficking pathways. As shown for other regulatory proteins such as adaptors, the involvement of protein motors in CFTR traffic is cell-type specific. Understanding motor specificity provides insight into the biology of the channel and opens opportunity for discovery of organ-specific drug targets for treating CFTR-mediated diseases.

Figure 1

Motor transport systems involved in CFTR exocytosis in the airway and intestinal epithelium. CFTR (red) is localized to the apical domain of airway and intestinal epithelial cells. In airway epithelium, CFTR decorates the apical plasma membrane in the inter-ciliary space and subapical region, while in the intestinal epithelium CFTR is in the subapical cytoplasm, intermicrovillar and microvillar membranes. Brackets show the predominant type of transport associated with the apical delivery of CFTR. Nuclei are shown in beige, cytosol in light blue and Golgi apparatus in green. The insets A–D indicate the motors that move CFTR in the particular region of the cells, highlighted with squares. (A) MT-associated motor kinesin moves CFTR-associated vesicle up the microtubule in the intestinal epithelial cell; (B) Myo5b moves exocytic CFTR-associated vesicle on microfilaments in airway and intestinal epithelial cells; (C) Myo6 facilitates endocytosis of CFTR in airway and intestine; (D) Myo1a is important for the exocytosis and, probably, tethering of microvillar membrane-inserted CFTR in the enterocyte. Microtubule is shown in yellow, microfilaments in dark blue and PM-inserted CFTR in red. Upward arrows facing indicate exocytosis, downward arrow–endocytosis.