Figure 2

CFTR is co-translationally inserted into the ER membrane during ribosomal translation of CFTR mRNA from the nucleus. If CFTR is misfolded in the ER it is ubiquitylated and retrotranslocated to the cytosol, where it is degraded by the 26S proteasome. Upon inhibition of the proteasome, ubiquitylated CFTR is localized to a pericentriolar aggresome structure. Correctly folded CFTR proteins are transferred to the Golgi apparatus for glycolytic maturation via the coat complex II (COPII) machinery. Mature CFTR is exported to the plasma membrane to function as a chloride ion channel. CFTR protein levels at the plasma membrane are regulated by sub-apical vesicles delivering CFTR protein for either lysosomal degradation or recycling. For simplicity, we have represented CFTR with a single membrane spanning sepia symbol. Readers are invited to refer to figures 1 and 3 for the full domain architecture of the protein.