[Frontiers in Bioscience S4, 1088-1098 , January 1, 2012]

Sensory functions of motile cilia and implication for bronchiectasis

Raksha Jain1,2, Cylen Javidan-Nejad3, Jennifer Alexander-Brett1, Amjad Horani4, Michele C. Cabellon1, Michael J. Walter1, Steven L. Brody1

1Departments of Medicine, 3Radiology and 4Pediatrics, Washington University School of Medicine, St. Louis, MO, 63110, USA, 2Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1.Classes of cilia
2.2.Sensory cilia
3. Ciliopathies
3.1. Motile ciliopathies
3.2. Primary cilia syndromes
4. Evidence for sensory function in motile cilia
4.1. Evolutionary considerations
4.2. Shared motor and sensory functions in motile invertebrate cilia
5. Experimental evidence for shared motile and sensory function in vertebrates
5.1. Transient receptor potential cation channel subfamily V member 4 (TRPV4)
5.2. Bitter taste receptors (T2R)
5.3. Progesterone receptor (PR)
5.4. Vang like 2 (VANGL2)
5.5. Polycystin-1 (PKD1) and polycystin-2 (PKD2)
5.6. PKD1 and PKD2 expression in motile cilia
6. Radiographic Bronchiectasis in ADPKD
6.1. Multisystem features of ADPKD
6.2. ADPKD cohort for study of bronchiectasis
6.3. Scoring radiographic bronchiectasis in ADPKD
6.4. Clinical features and risk factors for bronchiectasis in ADPKD
6.5. Bronchiectasis in ADPKD patients following renal transplantation
7. Summary and Perspective: Lung disease and sensory function in motile cilia
7.1. The etiology of bronchiectasis in ADPKD
7.2. A shared role for cilia sensory signaling to regulate beat frequency
7.3. Modeling cilia sensory feedback in lung health and disease
8. Acknowledgements
9. References

1. 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 proteincomplex, 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.