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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2018 Apr 24

PMID 29681531

Citations 90

Authors

Zhongming Ma

Akiyuki Taruno

Makoto Ohmoto

Masafumi Jyotaki

Jason C Lim

Hiroaki Miyazaki

Naomi Niisato

Yoshinori Marunaka

Robert J Lee

Henry Hoff

Riley Payne

Angelo Demuro

Ian Parker

Claire H Mitchell

Jorge Henao-Mejia

Jessica E Tanis

Ichiro Matsumoto

Michael G Tordoff

J Kevin Foskett

Affiliations

Soon will be listed here.

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.

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