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CELL SIGNALING PROCESSES IN TASTE CELLS

CELL SIGNALING PROCESSES IN TASTE CELLS. KATHRYN MEDLER LAB. Why should we care about taste?. Taste is used to determine if potential food items will be ingested or rejected. Taste is used by all organisms and is the oldest sensory system.

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CELL SIGNALING PROCESSES IN TASTE CELLS

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  1. CELL SIGNALING PROCESSES IN TASTE CELLS KATHRYN MEDLER LAB

  2. Why should we care about taste? Taste is used to determine if potential food items will be ingested or rejected. Taste is used by all organisms and is the oldest sensory system. Loss of taste can lead to depression and loss of appetite which can cause malnutrition. Deficits in the taste system can also lead to uncontrolled appetite and obesity.

  3. Mammalian taste buds are present in papillae on the tongue Taste stimuli Apical Lingual Epithelium Taste bud Basolateral Afferent gustatory nerve fiber

  4. Taste Transduction: Two distinct signaling pathways exist H+ Na+ + + + Ca2+ Store Na+ [Ca2+]i Ca2+ [Ca2+]i K+ Multiple signaling pathways are present taste cells and all pathways depend on increases in intracellular calcium to transmit signals to the nervous system. Our lab is studying these different signaling mechanisms: how they function and how they are regulated. Bitter Sweet Umami R PLC IP3 TRPM5 Serotonin ATP

  5. Calcium imaging measures changes in calcium levels in live cells We can characterize the functional role of different proteins expressed in these cells and how they affect calcium signals.

  6. Using calcium imaging we found: “Ionic” stimuli “Complex” stimuli Activate calcium release from stores Activate voltage gated calcium influx Different taste stimuli evoke different signals. Hacker et al., 2008

  7. Surprisingly, we also found Some taste cells responded to bitter stimuli AND cell depolarization. Hacker et al., 2008 This is a newly identified sub-population of taste cells.

  8. We asked the question: How do these taste cells respond to multiple stimuli?

  9. Expression patterns of PLCb3/IP3R1 in taste cells D PLCb3 and IP3R1 are co-expressed in a population of taste cells that are distinct from the PLCb2 expressing cells. Further studies are being conducted to characterize this newly identified signaling pathway.

  10. There are 3 separate taste cell groups. We are asking “How do each of these groups contribute to detection of taste stimuli?”

  11. We are also studying the evoked taste responses in obese mice. We asked “Are peripheral taste responses different in obese mice versus normal mice?” The number of responsive taste cells and the response amplitudes are reduced in obese mice for the appetitive tastes. We’re asking how does this affect the animal’s ability to perceive taste stimuli? Is it reversible?

  12. We recently identified a new TRP channel in taste cells. TRPM5 is a well-known monovalent selective TRP channel that is important in taste transduction. TRPM5 turns on in response to some taste stimulation. We found that taste cells also express TRPM4, which is the other monovalent selective TRP channel. TRPM4 is also activated by some taste stimuli.

  13. We are determining the role of TRPM4 in taste transduction. In some cells, taste stimuli evoke sodium and calcium increases. Using imaging and patch clamp, we’re determining how TRPM4 contributes to these responses.

  14. Gene regulation by WT1 in taste cells In collaboration with Stefan Roberts lab

  15. Transcriptional Regulation by WT1 BASP1 General transcription machinery IIH IIE IIF Pol II IIB WT1 IID IIA TATA Growth factors Amphiregulin IGFII PDGF-A Apoptosis Bcl 2 Bak c-myc Differentiation Podocalyxin Nephrin

  16. WT1 plays a critical role in the development of several organs and tissues WT1 Knock-out mice Kidneys Gonads Spleen Adrenal glands Diaphragm Retinal Ganglia Olfactory epithelium Taste buds

  17. WT1 and BASP1 are expressed in taste cells Embryonic Adult WT1 Ctrl WT1 BASP1 Ctrl E13 E14.5 E17.5

  18. WT1 null mice fail to develop a peripheral taste system E13.5 WT WT Troma 1 Sox2 KO KO WT WT GAP-43 Shh KO KO

  19. WT1 regulates genes critical for taste cell development Real time PCR * LEF1 CHiP assay Relative mRNA WT KO * PTCH1 Relative mRNA WT KO BMP4 *

  20. Primary taste cells can be cultured and transfected Hoechst Hoechst CHiP qPCR Hoechst WT1 PLCβ2 TRMP5-GFP Knockdown of WT1 in cultured taste buds causes a reduction in the expression of WT1 target genes that are important in taste cell maintenance.

  21. Combine the physiological and molecular approaches of the Medler and Roberts labs to study the role of WT1 and BASP1 in gene regulation during development and tissue homeostasis

  22. If you are interested in rotating in the lab on any of these projects, please contact me by email: kmedler@buffalo.edu

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