Skip to main content

Advertisement

Log in

The c-kit Receptor Tyrosine Kinase Marks Sweet or Umami Sensing T1R3 Positive Adult Taste Cells in Mice

  • Published:
Chemosensory Perception

Abstract

Introduction

Previous studies have described a number of protein tyrosine kinases (epidermal growth factor receptor, ErbB2, ErbB3, and c-kit) to be expressed in taste bud cells, their innervating nerves, and in developing taste papillae.

Methods

Immunohistochemical staining of mouse taste buds was performed to characterize the expression patterns of the c-kit receptor in taste.

Results

Here we demonstrate that c-kit positive cells are exclusively co-localized with T1R3 (which forms one half of the receptors for sweet and umami taste) in adult taste cells.

Conclusions

This implies that c-kit+ cells are primarily taste cells that respond to sweet and umami, but not to bitter, sour, or salty. These data indicate that the control of c-kit activation may be important for proper taste bud formation and may aid in the maintenance of this specific mature taste cell subpopulation.

Implications

Further characterization of the functional role of c-kit in taste may lead to superior taste cell cultures or organoids, and elucidate mechanisms of taste cell regulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

References

  • Adams VR, Leggas M (2007) Sunitinib malate for treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Clin Ther 29:1338–1353

    Article  CAS  Google Scholar 

  • Bartel DL, Sullivan SL, Lavoie EG, Sévigny J, Finger TE (2006) Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J Comp Neurol 497:1–12

    Article  CAS  Google Scholar 

  • Beidler LM, Smallman RL (1965) Renewal of cells within taste buds. J Cell Biol 27:263–272

    Article  CAS  Google Scholar 

  • Biggs BT, Tang T, Krimm RF (2016) Insulin-like growth factors are expressed in the taste system, but do not maintain adult taste buds. PLoS One 11(2):e0148315

    Article  Google Scholar 

  • Bigiani A (2001) Mouse taste cells with glialike membrane properties. J Neurophysiol 85(4):1552–1560

    Article  CAS  Google Scholar 

  • Chaudhari N, Roper SD (2010) The cell biology of taste. J Cell Biol 190:285–296

    Article  CAS  Google Scholar 

  • Copeland NG, Gilbert DJ, Cho BC, Donovan PJ, Jenkins NA, Cosman D, Anderson D, Lyman SD, Williams DE (1990) Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 63:175–183

    Article  CAS  Google Scholar 

  • Cruz AC, Frank BT, Edwards ST, Dazin PF, Peschon JJ, Fang KC (2003) Tumor necrosis factor-alpha converting enzyme controls surface expression of c-kit and survival of embryonic stem cell-derived mast cells. J Biol Chem 279:5612–5620

    Article  Google Scholar 

  • Dando R, Pereira E, Kurian M, Barro-Soria R, Chaudhari N, Roper SD (2015) A permeability barrier surrounds taste buds in lingual epithelia. Am J Phys Cell Phys 308(1):C21–C32

    Article  CAS  Google Scholar 

  • Fang S, Wei J, Pentinmikko N, Leinonen H, Salven P (2012) Generation of functional blood vessels from a single c-kit+ adult vascular endothelial stem cell. PLoS Biol 10(10):e1001407

    Article  CAS  Google Scholar 

  • Farbman AI (1980) Renewal of taste bud cells in rat circumvallate papillae. Cell Tissue Kinet 13:349–357

    CAS  PubMed  Google Scholar 

  • Feng P, Zhao H, Chai J, Huang L, Wang H (2012) Expression and secretion of TNF-alpha in mouse taste buds: a novel function of a specific subset of type II taste cells. PLoS One 7:e43140

    Article  CAS  Google Scholar 

  • Feng P, Chai J, Zhou M, Simon N, Huang L, Wang H (2014) Interleukin-10 is produced by a specific subset of taste receptor cells and critical for maintaining structural integrity of mouse taste buds. J Neurosci 34(7):2689–2701

    Article  CAS  Google Scholar 

  • Finger TE (2005) Cell types and lineages in taste buds. Chem Senses 30(Suppl 1):i54–i55

    Article  Google Scholar 

  • Goldstein BJ, Goss GM, Hatzistergos KE, Rangel EB, Seidler B, Saur D, Hare JM (2015) Adult c-kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. J Comp Neurol 523(1):15–31

    Article  CAS  Google Scholar 

  • Goodman VL, Rock EP, Dagher R, Ramchandani RP, Abraham S, Gobburu JVS et al (2007) Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res 13:1367–1373

    Article  CAS  Google Scholar 

  • Goss GM, Chaudhari N, Hare JM, Nwojo R, Seidler B, Saur D, Goldstein BJ (2016) Differentiation potential of individual olfactory c-Kit+ progenitors determined via multicolor lineage tracing. Dev Neurobiol 76(3):241–251

    Article  CAS  Google Scholar 

  • Hevezi P, Moyer BD, Lu M, Gao N, White E, Echeverri F, Kalabat D, Soto H, Laita B, Li C, Yeh SA, Zoller M, Zlotnik A (2009) Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes. PLoS One 4(7):e6395

    Article  Google Scholar 

  • Huang YA, Maruyama Y, Stimac R, Roper SD (2008) Presynaptic (type III) cells in mouse taste buds sense sour (acid) taste. J Physiol 586(12):2903–2912

    Article  CAS  Google Scholar 

  • Kaufman A, Choo E, Koh A, Dando R (2018) Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLoS Biol 16(3):e2001959

    Article  Google Scholar 

  • Kaufman A, Kim J, Noel C, Dando R (2019) Taste loss with obesity in mice and men. Int J Obes:1–5

  • Krishnamurthy M, Ayazi F, Li J, Lyttle AW, Woods M, Wu Y, Yee SP, Wang R (2007) c-Kit in early onset of diabetes: a morphological and functional analysis of pancreatic beta-cells in c-KitW-v mutant mice. Endocrinology 148:5520–5530

    Article  CAS  Google Scholar 

  • Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R (2005) Normal and oncogenic forms of the receptor tyrosine kinase kit. Stem Cells 23:16–43

    Article  CAS  Google Scholar 

  • Liang J, Wu Y-L, Chen B-J, Zhang W, Tanaka Y, Sugiyama H (2013) The c-kit receptor-mediated signal transduction and tumor-related diseases. Int J Biol Sci 9(5):435–443

    Article  Google Scholar 

  • Linnekin D (1999) Early signaling pathways activated by c-kit in hematopoietic cell. Int J Biochem Cell Biol 31:1053–1074

    Article  CAS  Google Scholar 

  • Liu SL, Chen G, Zhao YP, Wu WM, Zhang TP (2013) Optimized dose of imatinib for treatment of gastrointestinal stromal tumors: a meta-analysis. J Dig Dis 14(1):16–21

    Article  CAS  Google Scholar 

  • Luo L, Urata Y, Yan C, Hasan AD, Goto S, Guo CY, Tou FF, Xie Y, Li TS (2016) Radiation exposure decreases the quantity and quality of cardiac stem cells in mice. PLoS One 11(5):e0152179

    Article  Google Scholar 

  • McLaughlin SK (2000) Erb and c-Kit receptors have distinctive patterns of expression in adult and developing taste papillae and taste buds. J Neurosci 20:5679–5688

    Article  CAS  Google Scholar 

  • Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I (2009) Sweet taste receptor expressed in pancreatic β-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One 4(4):e5106

    Article  Google Scholar 

  • Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106(3):381–390

    Article  CAS  Google Scholar 

  • Noel CA, Cassano PA, Dando R (2017) College-aged males experience attenuated sweet and salty taste with modest weight gain. J Nutr 147(10):1885–1891

    Article  CAS  Google Scholar 

  • Okubo T, Pevny LH, Hogan BL (2006) Sox2 is required for development of taste bud sensory cells. Genes Dev 20(19):2654–2659

    Article  CAS  Google Scholar 

  • Perea-Martinez I, Nagai T, Chaudhari N (2013) Functional cell types in taste buds have distinct longevities. PLoS One 8(1):e53399

    Article  CAS  Google Scholar 

  • Reber L, Da Silva CA, Frossard N (2006) Stem cell factor and its receptor c-Kit as targets for inflammatory diseases. Eur J Pharmacol 533:327–340

    Article  CAS  Google Scholar 

  • Tomchik SM, Berg S, Kim JW, Chaudhari N, Roper SD (2007) Breadth of tuning and taste coding in mammalian taste buds. J Neurosci 27(40):10840–10848

    Article  CAS  Google Scholar 

  • Vandenbeuch A, Clapp TR, Kinnamon SC (2008) Amiloride-sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci 9(1):1

    Article  Google Scholar 

  • Wang H, Iguchi N, Rong Q, Zhou M, Ogunkorode M, Inoue M, Pribitkin EA, Bachmanov AA, Margolskee RF, Pfeifer K, Huang L (2009) Expression of the voltage-gated potassium channel KCNQ1 in mammalian taste bud cells and the effect of its null-mutation on taste preferences. J Comp Neurol 512(3):384–398

    Article  CAS  Google Scholar 

  • Wang L, Wang J, Li Z, Liu Y, Jiang M, Li Y, Cao D, Zhao M, Wang F, Luo F (2016) Silencing stem cell factor attenuates stemness and inhibits migration of cancer stem cells derived from Lewis lung carcinoma cells. Tumour Biol 37:7213–7227

    Article  Google Scholar 

  • Williams DE, Eisenman J, Baird A, Rauch C, Van Ness K, March CJ, Park LS, Martin U, Mochizuki DY, Boswell HS et al (1990) Identification of a ligand for the c-kit proto-oncogene. Cell 63:167–174

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Michael Kotlikoff of Cornell University for providing c-kit-eGFP+ reporter mice for initial experiments.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception, design, and writing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Robin Dando.

Ethics declarations

Conflict of Interest

Authors declare no conflict of interest.

Ethical Approval

Experiments were conducted with approval from the Institutional Animal Care and Use Committee at Cornell University (approval no. 2012-0080).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(DOCX 11568 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choo, E., Dando, R. The c-kit Receptor Tyrosine Kinase Marks Sweet or Umami Sensing T1R3 Positive Adult Taste Cells in Mice. Chem. Percept. 14, 41–46 (2021). https://doi.org/10.1007/s12078-019-09277-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12078-019-09277-5

Keywords

Navigation