{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:41:10Z","timestamp":1774982470074,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K08490"],"award-info":[{"award-number":["16K08490"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08531"],"award-info":[{"award-number":["17K08531"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K15029"],"award-info":[{"award-number":["15K15029"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020051","name":"Tamura Science and Technology Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012036","name":"Lotte Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012036","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bitterness is an important physiological function in the defense responses to avoid toxic foods. The taste receptor 2 family is well known to mediate bitter taste perception in Type II taste cells. Here, we report that the polycystic kidney disease 2-like 1 (PKD2L1) channel is a novel sensor for the bitter aftertaste in Type III taste cells. The PKD2L1 channel showed rebound activation after the washout of quinine, a bitter tastant, in electrophysiological whole-cell recordings of the PKD2L1-expressing HEK293T cells and Ca<jats:sup>2+<\/jats:sup>-imaging analysis of Type III taste cells isolated from wild-type PKD2L1 mice. In the short-term two-bottle preference and lick tests in vivo, the wild-type mice avoided normal water while the PKD2L1-knockout mice preferred normal water after they ingested the quinine-containing water. These results may explain the new mechanism of the quinine-triggered bitter aftertaste perception in Type III taste cells.<\/jats:p>","DOI":"10.1038\/s41598-023-31322-3","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T17:04:34Z","timestamp":1678899874000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Polycystic kidney disease 2-like 1 channel contributes to the bitter aftertaste perception of quinine"],"prefix":"10.1038","volume":"13","author":[{"given":"Takahiro","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuto","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Hanita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Shinozaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusaku","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiro","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teppei","family":"Kageyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisao","family":"Nishijo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Tominaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"31322_CR1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3803\/EnM.2021.302","volume":"36","author":"JH Jang","year":"2021","unstructured":"Jang, J. H., Kwon, O., Moon, S. J. & Jeong, Y. T. Recent advances in understanding peripheral taste decoding I: 2010 to 2020. Endocrinol. Metab. 36, 469\u2013477 (2021).","journal-title":"Endocrinol. Metab."},{"key":"31322_CR2","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S0092-8674(00)80705-9","volume":"100","author":"E Adler","year":"2000","unstructured":"Adler, E. et al. A novel family of mammalian taste receptors. Cell 100, 693\u2013702 (2000).","journal-title":"Cell"},{"key":"31322_CR3","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/S0092-8674(00)80706-0","volume":"100","author":"J Chandrashekar","year":"2000","unstructured":"Chandrashekar, J. et al. T2Rs function as bitter taste receptors. Cell 100, 703\u2013711 (2000).","journal-title":"Cell"},{"key":"31322_CR4","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/35007072","volume":"404","author":"H Matsunami","year":"2000","unstructured":"Matsunami, H., Montmayeur, J. P. & Buck, L. B. A family of candidate taste receptors in human and mouse. Nature 404, 601\u2013604 (2000).","journal-title":"Nature"},{"key":"31322_CR5","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nature03352","volume":"434","author":"KL Mueller","year":"2005","unstructured":"Mueller, K. L. et al. The receptors and coding logic for bitter taste. Nature 434, 225\u2013229 (2005).","journal-title":"Nature"},{"key":"31322_CR6","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1083\/jcb.201003144","volume":"190","author":"N Chaudhari","year":"2010","unstructured":"Chaudhari, N. & Roper, S. D. The cell biology of taste. J. Cell Biol. 190, 285\u2013296 (2010).","journal-title":"J. Cell Biol."},{"key":"31322_CR7","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1093\/molbev\/msg083","volume":"20","author":"P Shi","year":"2003","unstructured":"Shi, P., Zhang, J., Yang, H. & Zhang, Y. P. Adaptive diversification of bitter taste receptor genes in mammalian evolution. Mol. Biol. Evol. 20, 805\u2013814 (2003).","journal-title":"Mol. Biol. Evol."},{"key":"31322_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00424-020-02464-4","volume":"473","author":"A Taruno","year":"2021","unstructured":"Taruno, A. et al. Taste transduction and channel synapses in taste buds. Pfl\u00fcg. Arch. 473, 3\u201313 (2021).","journal-title":"Pfl\u00fcg. Arch."},{"key":"31322_CR9","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1152\/physrev.00021.2006","volume":"87","author":"B Nilius","year":"2007","unstructured":"Nilius, B., Owsianik, G., Voets, T. & Peters, J. A. Transient receptor potential cation channels in disease. Physiol. Rev. 87, 165\u2013217 (2007).","journal-title":"Physiol. Rev."},{"key":"31322_CR10","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1093\/chemse\/bjm083","volume":"33","author":"S Kataoka","year":"2008","unstructured":"Kataoka, S. et al. The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse. Chem. Senses 33, 243\u2013254 (2008).","journal-title":"Chem. Senses"},{"key":"31322_CR11","doi-asserted-by":"publisher","first-page":"12569","DOI":"10.1073\/pnas.0602702103","volume":"103","author":"Y Ishimaru","year":"2006","unstructured":"Ishimaru, Y. et al. Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc. Natl. Acad. Sci. U. S. A. 103, 12569\u201312574 (2006).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"31322_CR12","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/nature05084","volume":"442","author":"AL Huang","year":"2006","unstructured":"Huang, A. L. et al. The cells and logic for mammalian sour taste detection. Nature 442, 934\u2013938 (2006).","journal-title":"Nature"},{"key":"31322_CR13","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/embor.2008.89","volume":"9","author":"H Inada","year":"2008","unstructured":"Inada, H. et al. Off-response property of an acid-activated cation channel complex PKD1L3-PKD2L1. EMBO Rep. 9, 690\u2013697 (2008).","journal-title":"EMBO Rep."},{"key":"31322_CR14","doi-asserted-by":"publisher","first-page":"17277","DOI":"10.1074\/jbc.C110.132944","volume":"285","author":"H Kawaguchi","year":"2010","unstructured":"Kawaguchi, H. et al. Activation of polycystic kidney disease-2-like 1 (PKD2L1)-PKD1L3 complex by acid in mouse taste cells. J. Biol. Chem. 285, 17277\u201317281 (2010).","journal-title":"J. Biol. Chem."},{"key":"31322_CR15","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/chemse\/bjq070","volume":"35","author":"TM Nelson","year":"2010","unstructured":"Nelson, T. M. et al. Taste function in mice with a targeted mutation of the Pkd1l3 gene. Chem. Senses 35, 565\u2013577 (2010).","journal-title":"Chem. Senses"},{"key":"31322_CR16","doi-asserted-by":"publisher","first-page":"e20007","DOI":"10.1371\/journal.pone.0020007","volume":"6","author":"N Horio","year":"2011","unstructured":"Horio, N. et al. Sour taste responses in mice lacking PKD channels. PLoS ONE 6, e20007 (2011).","journal-title":"PLoS ONE"},{"key":"31322_CR17","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s00424-011-0934-5","volume":"461","author":"T Shimizu","year":"2011","unstructured":"Shimizu, T., Higuchi, T., Fujii, T., Nilius, B. & Sakai, H. Bimodal effect of alkalization on the polycystin transient receptor potential channel, PKD2L1. Pfl\u00fcg. Arch. 461, 507\u2013513 (2011).","journal-title":"Pfl\u00fcg. Arch."},{"key":"31322_CR18","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1007\/s00424-013-1439-1","volume":"466","author":"T Higuchi","year":"2014","unstructured":"Higuchi, T., Shimizu, T., Fujii, T., Nilius, B. & Sakai, H. Gating modulation by heat of the polycystin transient receptor potential channel PKD2L1 (TRPP3). Pfl\u00fcg. Arch. 466, 1933\u20131940 (2014).","journal-title":"Pfl\u00fcg. Arch."},{"key":"31322_CR19","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1002\/2211-5463.12273","volume":"7","author":"T Shimizu","year":"2017","unstructured":"Shimizu, T. et al. The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage-dependent inactivation. FEBS Open Bio 7, 1392\u20131401 (2017).","journal-title":"FEBS Open Bio"},{"key":"31322_CR20","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1211\/jpp.59.11.0009","volume":"59","author":"T Akiyoshi","year":"2007","unstructured":"Akiyoshi, T. et al. Effects of quinine on the intracellular calcium level and membrane potential of PC 12 cultures. J. Pharm. Pharmacol. 59, 1521\u20131526 (2007).","journal-title":"J. Pharm. Pharmacol."},{"key":"31322_CR21","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1093\/hmg\/ddv484","volume":"25","author":"G Yao","year":"2016","unstructured":"Yao, G. et al. Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability. Hum. Mol. Genet. 25, 448\u2013458 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"31322_CR22","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1093\/chemse\/24.1.19","volume":"24","author":"G Neely","year":"1999","unstructured":"Neely, G. & Borg, G. The perceived intensity of caffeine aftertaste: tasters versus nontasters. Chem. Senses 24, 19\u201321 (1999).","journal-title":"Chem. Senses"},{"key":"31322_CR23","doi-asserted-by":"publisher","first-page":"e13413","DOI":"10.7554\/eLife.13413","volume":"5","author":"PG DeCaen","year":"2016","unstructured":"DeCaen, P. G., Liu, X., Abiria, S. & Clapham, D. E. Atypical calcium regulation of the PKD2-L1 polycystin ion channel. Elife 5, e13413 (2016).","journal-title":"Elife"},{"key":"31322_CR24","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s00424-008-0558-6","volume":"457","author":"T Shimizu","year":"2009","unstructured":"Shimizu, T., Janssens, A., Voets, T. & Nilius, B. Regulation of the murine TRPP3 channel by voltage, pH, and changes in cell volume. Pfl\u00fcg. Arch. 457, 795\u2013807 (2009).","journal-title":"Pfl\u00fcg. Arch."},{"key":"31322_CR25","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.3389\/fphys.2019.01267","volume":"10","author":"S Grassin-Delyle","year":"2019","unstructured":"Grassin-Delyle, S. et al. Bitter taste receptors (TAS2Rs) in human lung macrophages: Receptor expression and inhibitory effects of TAS2R agonists. Front. Physiol. 10, 1267 (2019).","journal-title":"Front. Physiol."},{"key":"31322_CR26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/j.1469-7793.1999.0397m.x","volume":"519","author":"T Tsunenari","year":"1999","unstructured":"Tsunenari, T., Kurahashi, T. & Kaneko, A. Activation by bitter substances of a cationic channel in membrane patches excised from the bullfrog taste receptor cell. J. Physiol. 519, 397\u2013404 (1999).","journal-title":"J. Physiol."},{"key":"31322_CR27","doi-asserted-by":"publisher","first-page":"536","DOI":"10.3389\/fphar.2017.00536","volume":"8","author":"E Patrono","year":"2017","unstructured":"Patrono, E. et al. Rewarding effects of operant dry-licking behavior on neuronal firing in the nucleus accumbens core. Front. Pharmacol. 8, 536 (2017).","journal-title":"Front. Pharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-31322-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-31322-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-31322-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T17:16:53Z","timestamp":1678900613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-31322-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["31322"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-31322-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]},"assertion":[{"value":"23 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4271"}}