The cystic fibrosis transmembrane conductance regulator's expanding SNARE interactome

The cystic fibrosis transmembrane conductance regulator (CFTR) interacts with multiple N-ethylmaleimide sensitive factor attachment protein (SNARE) molecules largely via its N-terminal cytoplasmic domain. The earliest known among these SNAREs are the cognate Q-SNARE pair of Syntaxin 1A (STX1A) and SNAP23 on the plasma membrane. These SNAREs affect CFTR chloride channel gating. CFTR exocytosis/recycling in intestinal epithelial cells is dependent on another SNARE located in the apical plasma membrane, STX3. Members of the STX8/STX7/vesicle transport through interaction with t-SNAREs homolog 1b/VAMP8 SNARE complex, which function in early to late endosome/lysosome traffic, are all known to interact with CFTR. Two SNAREs, STX6 and STX16 that function at the trans-Golgi network (TGN), have now been revealed as members of the CFTR SNARE interactome. We summarize here the SNAREs that interact with CFTR and discuss the roles of these SNAREs in the intracellular trafficking of CFTR and CFTR-associated pathophysiology.