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Airway cilia taste toxins

Your sense of taste doesn't end in your mouth: Cilia lining airways leading to the lungs express taste receptors and alter their undulations in the presence of bitter chemicals, says a study linkurl:published;http://www.sciencemag.org/sciencexpress/recent.dtlwebsite online today (July 23)in __Science__. These cilia are linked to signaling pathways that regulate their motility, allowing epithelial tissues in airways to sense toxins or noxious compounds and help protect the lungs. Motile cilia

By | July 23, 2009

Your sense of taste doesn't end in your mouth: Cilia lining airways leading to the lungs express taste receptors and alter their undulations in the presence of bitter chemicals, says a study linkurl:published;http://www.sciencemag.org/sciencexpress/recent.dtlwebsite online today (July 23)in __Science__. These cilia are linked to signaling pathways that regulate their motility, allowing epithelial tissues in airways to sense toxins or noxious compounds and help protect the lungs.
Motile cilia on airway epithelial cells
Image: SEM by Tom Moninger
"This is the first paper that shows that motile cilia can have sensory function," said Gáspár Jékely, a cell and molecular biologist at the linkurl:Max Planck Institute for Developmental Biology;http://www.eb.tuebingen.mpg.de/research-groups/gaspar-jekely/curriculum-vitae in Tuebingen, Germany, who was not involved in the study. "That's really quite remarkable that you have structures that move around but are also intimately tied to signaling pathways." Primary cilia -- relatively immobile cellular extensions that play important roles in sight and olfaction -- have long been known to serve in sensory capacities, but motile cilia were thought only to wave (or "beat"), moving mucous through airways and ova down fallopian tubes, for example. linkurl:Alok Shah,;http://gss.grad.uiowa.edu/node/1857 a University of Iowa graduate student in the lab of linkurl:Michael Welsh;http://www.hhmi.org/research/investigators/welsh_bio.html and co-first-author on the paper, said that researchers typically thought of primary cilia as "the smart ones" while motile cilia were characterized as the "workhorses" of the cilia universe. "The motile cilia were thought to be, well, just motile and not much more," linkurl:Maxence Nachury,;http://med.stanford.edu/profiles/frdActionServlet?choiceId=printerprofile&fid=8391 a Stanford molecular and cell biologist who was not involved with the study, told __The Scientist__. Shah and his collaborators searched for sensory-related genes in samples of human airway epithelia, the cells that line the trachea and upper bronchi. They found several members of the T2R family, which senses and responds to bitter tastes, lurking in microarray expression data. Using antibodies to specific T2Rs, they singled out four specific receptors localized in cilia protruding from epithelial cells that line airways. "I was very surprised" by the results, Shah told __The Scientist__. "When I first saw that, I thought, 'Oh my God. What are taste receptors doing in the airways?'"
T2R receptors (red) colocalizing with
motile cilia (green)

Image: Alok Shah
Moreover, the team noticed that the four different T2Rs localized to different parts of a single cilia. "As far as I know, no one has seen different receptors of the same family localizing differentially like that." Shah said this differential localization may play a role in tweaking sensitivities or signaling pathways. To nail down the motile cilia's role in these signaling pathways, Shah subjected cultured airway epithelial tissues to several bitter compounds, including nicotine. "We found a very nice dose dependent increase in intracellular calcium" -- the hallmark of cell signaling cascades -- "in response to bitter compounds," Shah noted. This calcium boost was followed by increased rates of ciliary beating. The taste-sensing abilities of motile cilia could also lead to bitter compound-mimicking drugs that could target motile cilia to increase their beating to clear disrupted airways, as is common in cystic fibrosis. "This is a clear target that could be used to upregulate ciliary beating in the airways," said Jékely. Conversely, in asthma, where epithelial airway surfaces become inflamed and irritated, drugs targeting motile cilia could quell the inflammation. "If one could modulate the excitation at the surface of these cilia," said Nachury, "one could really have a way to dampen that reaction." Shah, who recently received his PhD and is now shopping for a postdoc position, said that much about the sensory role and molecular mechanisms of motile cilia is yet to be discovered. linkurl:Sudipto Roy,;http://zfin.org/cgi-bin/webdriver?MIval=aa-labview.apg&OID=ZDB-LAB-040720-1 a researcher at the Institute of Molecular and Cell Biology in Singapore, agreed. "It will not be too surprising if subsequent research shows that motile cilia act as signaling hubs for many other kinds of sensory pathways," Roy wrote in an email to __The Scientist__.
**__Related stories:__***linkurl:Did bitter tasters do better?;http://www.the-scientist.com/article/display/22740/
[26th July 2005]*linkurl:Bitter taste;http://www.the-scientist.com/article/display/20775/
[14th October 2002]*linkurl:Bitter-Sweet Research;http://www.the-scientist.com/article/display/12651/
[15th October 2001]
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Comments

Avatar of: anonymous poster

anonymous poster

Posts: 2

July 24, 2009

I found this article to be very interesting and at the same time, surprising. Cerca 25 years ago, when I visited a hospital emergency when I was having trouble breathing, I was told by a doctor there, that the cilia in my windpipe (or was it esophagus?) would be paralyzed/immobilized for cerca 1/2 hour with each cigarette that I smoked. This meant that the pollutants and toxins that were coming in, were not not getting moved out as well as they could have been, had I not been smoking at all. \nFrom what I gather from this article, nicotine can prompt more motility by the cilia? I somehow doubt that. If anyone can clarify this, I would be happy to read their ideas on how cilia help clear our air passageways, etc..

July 25, 2009

\nHi anonymous,\n\nWhat makes you doubt that "nicotine cam prompt more motility by cilia" ?. I think that the real possibility is there. I kind of remember, though my memory fails many times, that people have reported on the presence of neuronal nicotine acethylcoline receptors in non neuronal cells. \n\nI don?t remember if they looked for those receptors also in ciliated cells of your windpipe but Sha?s observation that, exposure of airway epithelial tissues to bitter substances and nicotine elicits a dose response increase in intracellular calcium that is followed by increases in ciliary beating, appears to be consistent with the presence and activation of those receptors, among others, in the respiratory system.\n\nJust random thoughts. Anyway, I guess that your trouble breathing due to smoking boosted your determination to stop the unhealthy habit, did it?.\n\n
Avatar of: Sam uttah

Sam uttah

Posts: 1

July 25, 2009

I liked these kind of stories always. I don't know much about this but still feel like reading.
Avatar of: Robert Cassidy

Robert Cassidy

Posts: 1

July 25, 2009

As a scientist, I must add that this study was carried out much like the best science usually is. It is a very straightforward, and dare I say, elegant study. The results fit in very well and tell an amazing story. \n\nIsn't it just fascinating how the body works? This is a great design for a novel mechanism. Kudos, Shah et al.
Avatar of: Michael Keating

Michael Keating

Posts: 6

July 26, 2009

I too thought that smoking disabled cilia. Having smoked from the age of 16 to 45, I can confirm that my cilia seemed to have ceased to function. Even now almost 20 years a non-smoker I detect no cilia function.
Avatar of: CHARLENE FOREST

CHARLENE FOREST

Posts: 1

July 27, 2009

It has been known for a long time that unicellular organisms, such as the green alga, Chlamydomonas, use their cilia (flagella) for both swimming and for signaling. Chlamydomonas has been used as a model system for studying cilia.
Avatar of: anonymous poster

anonymous poster

Posts: 1

July 28, 2009

Are there cilia on the cells that line the esophagus? as shown in your title:\n Airway cilia taste toxins \nResearchers discover a new sensory function in the cellular extensions that undulate in your esophagus
Avatar of: Alla Katsnelson

Alla Katsnelson

Posts: 17

July 28, 2009

Indeed, thanks for spotting the error. \n-Alla Katsnelson, news editor
Avatar of: ASMA YAGHI

ASMA YAGHI

Posts: 1

August 18, 2009

This is a very interesting article to me as I have always suspected that motile cilia do have sensory capabilities, but did not have the proof. Shah et al provided it. As for nicotine, nicotine's direct effect on respiratory cilia has been demonstrated before as being stimulatory (Hahn HL et al D.Clin Investig. 1992 Mar-Apr;70(3-4):244-51). Nicotine increases ciliary beat frequency by a direct effect on respiratory cilia, but we have to be careful about assuming that this is the only effect of cigarette smoke. Nicotine's major metabolite is cotinine and it circulates in smokers at high concentrations and its direct effect on motile cilia is actually inhibitory (Agius AMet al.Clin Otolaryngol Allied Sci. 1995 Oct; 20(5):465-9). I think the jury is still out on how nicotine or cotinine exactly work and what the final effects are on respiratory cilia. In our laboratory (Firestone Research Aerosol Laboratory, Hamilton, Ontario), we demonstrated that nasal cilia function is depressed in patients with chronic obstructive pulmonary disease. These patients are smokers/ex-smokers with 50 or more pack years (A Yaghi, G Cox, and M Dolovich. Ciliary Beat Frequency (CBF) of Nasal Epithelial Cell Cilia is Depressed in Subjects with Chronic Obstructive Pulmonary Disease (COPD) Am J Respir Crit Care Med vol. 177: A798, 2008).\n\n

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