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Department of Otolaryngology
 

Chemosensory Transduction Laboratory

Sue C. Kinnamon - PhD


Summary of the Lab's Work

Molecular Mechanisms of Taste Transduction and Signaling
How does the tongue tell the brain about taste? Research in our laboratory focuses on the mechanisms used by taste receptor cells to detect the sweet, salty, sour, bitter and umami tastes in the foods we eat. Kinnamon photo 1.jpgTaste receptor cells are housed in special end organs called taste buds, which are found in connective tissue papillae on the tongue and in the epithelium of the soft palate, esophagus and larynx. Taste cells, unlike other sensory receptors, appear to use a diversity of mechanisms for transduction. Salts and acids directly modulate ion channels to depolarize taste cells, while sweet stimuli, amino acids and bitter compounds bind to specific membrane receptors coupled to G proteins and second messenger signaling cascades. Several taste receptor proteins and downstream signaling effectors have been cloned, including the receptors for umami, sweet and bitter stimuli. We have several lines of transgenic mice expressing green fluorescent protein (GFP) in defined subsets of taste cells so that particular taste cells can be targeted for physiological experiments. Utilizing electrophysiology, calcium imaging, immunocytochemistry and molecular biology, we are examining the second messengers and ion channels involved in the transduction of taste stimuli.

Kinnamon Photo 2.jpgIn addition to the initial events in transduction, we are interested in how taste information is communicated to the nervous system. What is the taste cell transmitter and what regulates its release?
Our recent studies suggest that the so called Type II taste cells, those that express receptors for bitter, sweet, and umami taste stimuli, release ATP as a transmitter to activate taste nerve fibers (Finger et al., 2005). However, other transmitters have been identified, including serotonin, noradrenalin, and GABA, all expressed in the so called Type III cells. What is the role of these taste cells in signaling to the nervous system, and which transmitters are involved? We are currently using transgenic and knockout mice to address these questions.



Solitary Chemosensory Cells in the Airway

We have recently identified a population of scattered chemosensory cells in the epithelium of the upper airway that utilize taste receptor molecules to signal the presence of irritant substances that enter the nose and trachea. Kinnamon Photo 3.jpgThese airway chemosensory cells utilize T2R (bitter taste) receptors and associated downstream signaling effectors similar to those in taste buds. Yet this airway system does not give rise to taste sensations despite using a transduction cascade similar to taste buds. Bitter compounds activate the airway chemosensory cells which relay this information to pain fibers of the trigeminal nerve which activate protective airway responses (e.g. coughing, apnea), presumably to rid the airways of noxious substances (Kinnamon & Reynolds, 2009). In collaboration with the laboratory of T. Finger (Dept. Cell Devel. Biol.), we using transgenic mice expressing GFP in solitary chemoreceptor cells to determine what types of Kinnamon photo 4.jpgcompounds are detected by these cells and how these cells participate in protective airway reflexes. Recent studies have shown that these solitary chemosensory cells respond to quorum signaling molecules that pathogenic bacteria release to monitor their population density.
Thus the airway chemosensory cells serve as sentinels to guard the airways against invasion by irritants and pathogens. We have recently begun collaboration with Drs. Vijay Ramakrishnan and Todd Kingdom, Rhinologists in our Department, to investigate whether solitary chemosensory cells are present in human nasal tissue and if they play a role in sino-nasal diseases such as chronic rhinosinusitis and allergic rhinitis.

Our research is focused on two chemical sensory systems: the gustatory system and the trigeminal system. In the gustatory system, we are interested in how taste cells detect chemical stimuli, how stimuli are transduced into receptor potentials, and how this information is transmitted to gustatory afferent fibers. Studies on the trigeminal system include the function of solitary chemoreceptor cells in the nasal respiratory epithelium. These cells, which express elements of the bitter taste transduction cascade, are innervated by the trigeminal nerve. Solitary chemoreceptor cells detect noxious chemicals and pathogenic bacteria that enter the airways, provoking protective airway reflexes such as apnea and sneezing. We are interested in what compounds are detected by these cells, how the cells are activated, and how this information is transmitted to the trigeminal nerve.

Sue C. Kinnamon, PhD
PI (Joint appts. in Dept. of Cell and Developmental Biology; Dept. of Physiology and Biophysics)

Aurelie Vandenbeuch
Postdoc

Arian Baquero
Postdoc

Marco Tizzano
Postdoc

Catherine Anderson
PRA

Daniel Sanculi
PRA

Danielle Boisvert
PRA

Thomas Finger, PhD
Rocky Mountain Taste and Smell Center

Linda Barlow,PhD
Rocky Mountain Taste and Smell Center

Diego Restrepo
Dept. of Cell and Develop. Biol

Finger, T. E., Danilova, V., Barrows, J., Bartel, D. L., Vigers, A. J., Stone, L., Hellekant, G., and Kinnamon, S.C. (2005). ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495-1499.

Clapp, T. R., Medler, K. F., Damak, S., Margolskee, R. F., and Kinnamon, S.C. (2006). Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25. BMC Biol 4:7.

Tizzano, M., Gulbransen, B.D., Vandenbeuch, A, Clapp, T.R., Herman, J.P., Sibhatu, H.M., Churchill, M.E.A., Silver, W.L., Kinnamon, S.C., and Finger, T.E.(2009). Nasal chemosensory cells utilize bitter taste signalling to detect irritants and pathogenic Bacteria. PNAS 107:3210-5.

Vandenbeuch, A., Clapp, T. R., and Kinnamon, S.C. (2008). Amiloride-sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci 9:1-13.

Katoka S, Baquero A, Yang D, Shultz N, Vandembeuch A, Ravid K, Kinnamon SC, Finger TE. (2012). A2BR adenosine receptor modulates sweet taste in circumvallate taste buds. PLos One 7(1):e30032.

Barham HP, Cooper SE, Anderson CB, Tizzano M, Kingdom TT, Finger TE, Kinnanom SC, Ramakrishnan VR. (2013). Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa. Int. Forum Allergy Rhinology. doi. 10.1002/alr.21149. [Epub ahead of print]