Motile Cilia of Human Airway Epithelia Are Chemosensory

Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Science (Impact Factor: 33.61). 08/2009; 325(5944):1131-4. DOI: 10.1126/science.1173869
Source: PubMed


Cilia are microscopic projections that extend from eukaryotic cells. There are two general types of cilia; primary cilia serve
as sensory organelles, whereas motile cilia exert mechanical force. The motile cilia emerging from human airway epithelial
cells propel harmful inhaled material out of the lung. We found that these cells express sensory bitter taste receptors, which
localized on motile cilia. Bitter compounds increased the intracellular calcium ion concentration and stimulated ciliary beat
frequency. Thus, airway epithelia contain a cell-autonomous system in which motile cilia both sense noxious substances entering
airways and initiate a defensive mechanical mechanism to eliminate the offending compound. Hence, like primary cilia, classical
motile cilia also contain sensors to detect the external environment.

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    • "Role in epithelial cells As mentioned above, several T2R subtypes are expressed in human bronchial epithelial cells (Shah et al., 2009). Stimulation of these T2R subtypes induces an increase in the ciliary beat frequency, which in turn may accelerate the elimination of (i) noxious particular substances and (ii) bacteria colonizing the lungs (such as P. aeruginosa, which secretes a homoserine-lactone that activates T2Rs) (Shah et al., 2009). Lung infection with P. aeruginosa is a hallmark of late-stage cystic fibrosis , and so T2Rs might also be a target of interest in this context. "
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    ABSTRACT: The receptors involved in bitter taste perception (bitter taste receptors - T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tissues (such as the heart, gut, nasal cavity and lungs) and cell types (chemosensory, smooth muscle, endothelial, epithelial and inflammatory cells). Although it is still not clear whether endogenous T2R agonists exist, the T2R receptors recognize many natural and synthetic compounds, such as the acyl-homoserine lactones produced by bacteria, caffeine, chloroquine, and erythromycin. In the upper airways, T2Rs are involved in neurogenic inflammation and bacterial clearance. Their known effects in the lungs are exerted at three different levels. Firstly, T2R agonists increase the beating frequency of cilia on epithelial cells. Secondly, the T2Rs induce bronchial smooth muscle cells to relax. Thirdly, the T2R receptors expressed on immune cells (such as macrophages and mast cells) modulate production of pro-inflammatory mediators. Furthermore, T2R agonists are effective in inhibiting lung inflammation or smooth muscle contraction in ex vivo and asthma animal models, and are known to be involved in bacterial killing in the nasal cavity and enhancing lung function in humans. This review focuses on the pharmacology and physiological functions of T2R receptors in the upper and lower airways. It presents recently acquired knowledge suggesting that T2Rs may become valuable drug targets in the treatment of diseases such as asthma and chronic rhinosinusitis. Copyright © 2015. Published by Elsevier Inc.
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    • "The primary cilium is a solitary finger-like extension from the cell surface of most mammalian cell types, first reported in 1968. Although once thought to be vestigial or relegated to developmental activity, the primary cilium is now recognized for its functional significance in a diverse array of cellular events, ranging from centriole sequestration, inhibition of cell division, cell polarity, mechanosensitivity, chemosensitivity and receptormediate cell signaling (Shah et al., 2009; Bloodgood, 2010; Satir et al., 2010; Takeda and Narita, 2012; Knowles et al., 2013). It is interesting that for many years my laboratory observed a solitary cilium projecting from nonciliated cells of the efferent ductules (Fig. 8). "
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    • "er and Kinnamon , 2011 ) . They were found to participate in signal transduction during digestive and metabolic processes affecting absorption of bitter molecules in the gut ( Behrens and Meyerhof , 2011 ; Jeon et al . , 2011 ) . In humans , T2Rs are expressed in the nasal cavity where they help to identify bacteria and activate immune responses ( Shah et al . , 2009 ; Tizzano et al . , 2010 ) . Therefore , coelacanth T2Rs may also have very different functions besides or instead of taste . One bitter tasting substance vital for coelacanth life is urea . In general , teleost fish excrete nitrogenous waste ( ammonia ) directly into the water . Tetrapods dispose of toxic nitrogenous waste by convertin"
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    ABSTRACT: G-protein coupled chemosensory receptors (GPCR-CRs) aid in the perception of odors and tastes in vertebrates. So far, six GPCR-CR families have been identified that are conserved in most vertebrate species. Phylogenetic analyses indicate differing evolutionary dynamics between teleost fish and tetrapods. The coelacanth Latimeria chalumnae belongs to the lobe-finned fishes, which represent a phylogenetic link between these two groups. We searched the genome of L. chalumnae for GPCR-CRs and found that coelacanth taste receptors are more similar to those in tetrapods than in teleost fish: two coelacanth T1R2s co-segregate with the tetrapod T1R2s that recognize sweet substances, and our phylogenetic analyses indicate that the teleost T1R2s are closer related to T1R1s (umami taste receptors) than to tetrapod T1R2s. Furthermore, coelacanths are the first fish with a large repertoire of bitter taste receptors (58 T2Rs). Considering current knowledge on feeding habits of coelacanths the question arises if perception of bitter taste is the only function of these receptors. Similar to teleost fish, coelacanths have a variety of olfactory receptors (ORs) necessary for perception of water-soluble substances. However, they also have seven genes in the two tetrapod OR subfamilies predicted to recognize airborne molecules. The two coelacanth vomeronasal receptor families are larger than those in teleost fish, and similar to tetrapods and form V1R and V2R monophyletic clades. This may point to an advanced development of the vomeronasal organ as reported for lungfish. Our results show that the intermediate position of Latimeria in the phylogeny is reflected in its GPCR-CR repertoire. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: 1-12, 2013. © 2013 Wiley Periodicals, Inc.
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