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Neuron. 2018 May 2;98(3):547-561.e10. doi: 10.1016/j.neuron.2018.03.043. Epub 2018 Apr 19.

CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes.

Author information

1
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: zma@pennmedicine.upenn.edu.
2
Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
3
Monell Chemical Senses Center, Philadelphia, PA, USA.
4
Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
5
Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
6
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Otorhinolaryngology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
7
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
8
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA.
9
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
10
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
11
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: foskett@pennmedicine.upenn.edu.

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.

KEYWORDS:

ATP release; blue-native page; concatemer; hexamer; knockout; mouse; patch-clamp electrophysiology; single-molecule photobleaching; taste bud; voltage-gated

PMID:
29681531
PMCID:
PMC5934295
DOI:
10.1016/j.neuron.2018.03.043
[Indexed for MEDLINE]
Free PMC Article

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