Distinct localization of septin proteins to ciliary sub-compartments in airway epithelial cells

Mucociliary clearance of the airways is accomplished by cilia-mediated laminar mucus flow along the planar epithelial surface. Maintenance of the highly specific architecture of the ciliated airway epithelium with columnar-shaped epithelial cells and tightening of the epithelial barrier is mainly attributed to the F-actin cytoskeleton. Recently, members of the highly conserved family of septin proteins have been shown to play crucial roles in ciliated tissue. These GTP-binding proteins form hetero-oligomeric complexes and assemble higher-order cytoskeletal structures such as filaments, bundles and ring-like structures such as a membrane diffusion barrier at the ciliary base. Here we analyzed the subcellular and sub-ciliary localization of various septin proteins by immunofluorescence imaging of airway epithelial cells. In addition to cytoplasmic localization we found that septins are either enriched at the apical cell cortex including the ciliary bases (septin-2, -4, -6, and -7), or show axonemal staining (septin-2, -7, -9 and -11) or specifically localize to ciliary sub-compartments (septin-8 and -9). The distinct localization of septins suggests structural functions as cytoskeletal components and as elements of the mechanical barrier at the apical cell cortex. Furthermore, the tight association of septin-8 and -9 with the ciliary compartment indicates a possible involvement in cilia-specific functions and cilia-related diseases.