CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes.
CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes.
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DOI：
10.1016/j.neuron.2018.03.043
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发表时间：
2018-05-02
期刊：
影响因子：
16.2
通讯作者：
Foskett JK
中科院分区：
文献类型：
--
作者：
Ma Z;Taruno A;Ohmoto M;Jyotaki M;Lim JC;Miyazaki H;Niisato N;Marunaka Y;Lee RJ;Hoff H;Payne R;Demuro A;Parker I;Mitchell CH;Henao-Mejia J;Tanis JE;Matsumoto I;Tordoff MG;Foskett JK
甜味、鲜味和苦味促味剂与II型味蕾细胞（TBC）顶膜中的G蛋白偶联受体（GPCR）的结合触发动作电位，该动作电位激活电压门控非选择性离子通道以将ATP释放到介导味觉的味觉神经。虽然CALHM 1是ATP释放所必需的，但提供适合于动作电位依赖性神经传递的传导ATP释放机制的通道复合物的分子鉴定仍有待确定。在这里，我们表明，CALHM 3与CALHM 1相互作用的孔形成亚基在CALHM 1/CALHM 3六聚体通道，赋予它快速电压激活门控相同的ATP释放通道在体内。Calhm 3仅在II型TBC中与Calhm 1共表达，其基因缺失会消除味蕾中味觉诱发的ATP释放和GPCR介导的味觉感知。因此，CALHM 3与CALHM 1一起，对于在II型TBC中形成GPCR介导的味道所需的快速电压门控ATP释放通道是必需的。Ma等鉴定了CALHM 1/CALHM 3异源六聚体离子通道作为II型味蕾细胞响应GPCR介导的味道（包括甜、苦和鲜味物质）而释放ATP作为味觉神经元的神经递质的机制。
Binding of sweet, umami, and bitter tastants to G-protein coupled receptors (GPCR) 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 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.
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DOI：
10.1073/pnas.1204023109
发表时间：
2012-07-10
影响因子：
11.1
作者：
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