Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
5-2-2018
Publication Source
Neuron
Volume
98
Issue
3
Start Page
547
Last Page
561.e10
DOI
10.1016/j.neuron.2018.03.043
Abstract
Binding of sweet, umami, and bitter tastants to G protein-coupled receptors (GPCRs) in apical membranes of type II taste bud cells (TBCs) triggers action potentials that activate a voltage-gated nonselective ion channel to release ATP to gustatory nerves mediating taste perception. Although calcium homeostasis modulator 1 (CALHM1) is necessary for ATP release, the molecular identification of the channel complex that provides the conductive ATP-release mechanism suitable for action potential-dependent neurotransmission remains to be determined. Here we show that CALHM3 interacts with CALHM1 as a pore-forming subunit in a CALHM1/CALHM3 hexameric channel, endowing it with fast voltage-activated gating identical to that of the ATP-release channel in vivo. Calhm3 is co-expressed with Calhm1 exclusively in type II TBCs, and its genetic deletion abolishes taste-evoked ATP release from taste buds and GPCR-mediated taste perception. Thus, CALHM3, together with CALHM1, is essential to form the fast voltage-gated ATP-release channel in type II TBCs required for GPCR-mediated tastes. Ma et al. identify a CALHM1/CALHM3 hetero-hexameric ion channel as the mechanism by which type II taste bud cells release ATP as a neurotransmitter to gustatory neurons in response to GPCR-mediated tastes, including sweet, bitter, and umami substances. © 2018 Elsevier Inc.
Keywords
ATP release, blue-native page, concatemer, hexamer, knockout, mouse, patch-clamp electrophysiology, single-molecule photobleaching, taste bud, voltage-gated, Animals, Calcium Channels, Female, HEK293 Cells, HeLa Cells, Humans, Ion Channel Gating, Mice, Mice, Transgenic, Receptors, G-Protein-Coupled, Receptors, Purinergic, Synaptic Transmission, Taste, Taste Perception, Xenopus, adenosine triphosphate, calcium channel, calcium homeostasis modulator 1, calcium homeostasis modulator 3, G protein coupled receptor, ion channel, purinergic receptor, unclassified drug, voltage gated calcium channel, calcium channel, CALHM1 protein, mouse, G protein coupled receptor, purinergic receptor, action potential, activation constant, adult, animal cell, animal experiment, animal model, animal tissue, Article, bitter taste, calcium homeostasis, CALHM3 gene, cell activity, channel gating, controlled study, female, gene deletion, gene expression, gene interaction, gene location, HEK293T cell line, HeLa cell line, human, human cell, in vivo study, ion current, male, molecular interaction, mouse, Neuro-2a cell line, neurotransmission, nonhuman, priority journal, sweetness, taste, taste bud cell, umami, animal, HEK293 cell line, physiology, synaptic transmission, taste, transgenic mouse, Xenopus
Recommended Citation
Ma, Z., Taruno, A., Ohmoto, M., Jyotaki, M., Lim, J. C., Miyazaki, H., Niisato, N., Marunaka, Y., Lee, R. J., Hoff, H., Payne, R., Demuro, A., Parker, I., Mitchell, C. H., Henao-Mejia, J., Tanis, J. E., Matsumoto, I., Tordoff, M. G., & Foskett, K. J. (2018). CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes. Neuron, 98 (3), 547-561.e10. http://dx.doi.org/10.1016/j.neuron.2018.03.043
Date Posted: 10 February 2023
This document has been peer reviewed.