The proton channel OTOP1 is a sensor for the taste of ammonium chloride.
The proton channel OTOP1 is a sensor for the taste of ammonium chloride.
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DOI：
10.1038/s41467-023-41637-4
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发表时间：
2023-10-05
影响因子：
16.6
通讯作者：
Liman, Emily R.
中科院分区：
文献类型：
--
作者：
Liang, Ziyu;Wilson, Courtney E.;Teng, Bochuan;Kinnamon, Sue C.;Liman, Emily R.
铵（NH 4+）是氨基酸的分解产物，在高水平下可能是有毒的，可以通过生物体的味觉系统检测到，从C。elegans到人类，几十年来一直用于脊椎动物的味觉研究。在这里，我们报告，OTOP 1，一个质子选择性离子通道表达在酸味（III型）味觉受体细胞（TRC），作为传感器氯化铵（NH 4Cl）的功能。细胞外NH 4Cl在表达鼠OTOP 1（mOTOP 1）、人OTOP 1和OTOP 1的其他物种变体的HEK-293细胞中诱发大的剂量依赖性内向电流，这与其碱化细胞胞质溶胶的能力相关。mOTOP 1 tm 6-tm 7接头中保守的细胞内精氨酸残基（R292）突变特异性降低了对NH 4Cl相对于酸刺激的反应。在Otop 1 −/−小鼠品系中，从分离的III型TRCs或味觉神经测量的对NH 4Cl的味觉反应被强烈减弱或消除。小鼠对NH 4Cl的行为厌恶，在缺乏II型TRCs的Skn-1a−/−小鼠中减少，在Otop 1的双重敲除中完全消除。这些数据共同揭示了质子通道OTOP 1在介导NH 4Cl味道的主要成分和先前未描述的通道激活机制中的意想不到的作用。铵被人类和其他动物的化学感觉系统检测到，以指导回避或吸引行为。在这里，作者表明质子通道OTOP 1被铵激活，是小鼠铵味觉反应所需的，并确定了一个与铵敏感性有关的保守残基。
Ammonium (NH4+), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NH4Cl). Extracellular NH4Cl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NH4Cl relative to acid stimuli. Taste responses to NH4Cl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1−/− mouse strain. Behavioral aversion of mice to NH4Cl, reduced in Skn-1a−/− mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NH4Cl and a previously undescribed channel activation mechanism. Ammonium is detected by chemosensory systems of humans and other animals to guide avoidance or attractive behavior. Here, the authors show that the proton channel OTOP1 is activated by ammonium, is required for ammonium taste responses in mice, and identify a conserved residue involved in ammonium sensitivity.
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影响因子：
5.9
作者：
Li, Bin;Wang, Yan;Castro, Alexis;Ng, Courtney;Wang, Zhifei;Chaudhry, Haroon;Agbaje, Zainab;Ulloa, Gabriella A.;Yu, Yong
通讯作者：
Yu, Yong
酸味受体 Otopetrin1 的线虫同源物是进化上保守的酸敏感质子通道。
影响因子：
5.5
作者：
通讯作者：
--
影响因子：
5.9
作者：
Dhakal S;Sang J;Aryal B;Lee Y
通讯作者：
Lee Y
DOI：
10.1073/pnas.1013664107
发表时间：
2010-12-21
影响因子：
11.1
作者：
Chang, Rui B.;Waters, Hang;Liman, Emily R.
通讯作者：
Liman, Emily R.
影响因子：
3.7
作者：
Frokjaer-Jensen, Christian;Ailion, Michael;Lockery, Shawn R.
通讯作者：
Lockery, Shawn R.