Sensory functions of motile cilia and implication for bronchiectasis

Abstract

Cilia are specialized organelles that extend from the cell surface into the local environment. Cilia of the airway epithelia are motile to provide mucociliary clearance. On other cells, solitary cilia are specialized to detect chemical or mechanosensory signals. Sensory proteins in motile cilia have recently been identified that detect fluid flow, bitter taste and sex hormones. The relationship of these sensory functions in motile cilia to disease is now being revealed. An example are the polycystin-1 and polycystin-2 proteins that function as a flow sensor in kidney cilia and are mutated in autosomal dominant polycystic kidney disease (ADPKD). These polycystins are also expressed in motile cilia, potentially operating as sensors in the lung. Computed tomography studies from patients with ADPKD reveal evidence of bronchiectasis, suggesting polycystins are important in lung function. The motile cilia expression of this protein complex, as well as sensory channel TRPV4, bitter taste and sex hormones receptors, indicate that the cilia is wired to interpret environmental cues. Defective signaling of sensory proteins may result in a ciliopathy that includes lung disease.

Figure 1. Sensory functions of receptor molecules on motile cilia

Integration of experimental evidence for receptors identified on motile cilia, putative signaling pathways and function. Functions indicated by (?) are not specifically identified in motile cilia but are identified in primary cilia, or are not yet defined, as in the case of Vangl2.

Figure 2. Representative examples of radiographic bronchiectasis in patients with ADPKD

Computed tomography sections obtained approximately at the level of the mid lung fields. A. Lack of airway tapering (arrow) and dilated airways, grades 1 and 2, in the right and left lungs (arrowheads); B. Grade 1 wall thickening (arrow); C. Grade 1 airway dilation (arrows).

Figure 3. Model of sensory function in motile cilia in the airway

Cilia sensors act to provide continuous feedback to regulate cilia beat function, cilia orientation following cilia biogenesis during post-injury repair and potentially, ion and mucin components of airway surface liquid (ASL) (left). In response to environmental factors (center), there is enhanced activation of specialized sensors to trigger host response pathways. Impaired or mutated sensory protein or pathway results in features of disease (right).