Sarco/Endoplasmic reticulum Ca2+-ATPases (SERCA) contribute to GPCR-mediated taste perception.
Sarco/Endoplasmic reticulum Ca2+-ATPases (SERCA) contribute to GPCR-mediated taste perception.
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DOI：
10.1371/journal.pone.0023165
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Iguchi N;Ohkuri T;Slack JP;Zhong P;Huang L
味觉对于为动物提供有关食物质量的有价值的信息非常重要，例如营养或有害的自然。哺乳动物，包括人类，至少可以识别五种主要的味道：甜、鲜味(可口)、苦、酸和咸。最近的研究已经确定了味蕾细胞中味觉触发分子事件初始步骤的分子和机制，特别是正常味觉信号转导和传递所需的胞内游离钙浓度([Ca2+]c)的增加。然而，关于控制味觉感受器细胞(TrCs)胞浆中升高的[Ca~(2+)]c被清除的机制以及这些机制的破坏如何影响味觉，人们知之甚少。为了研究TRCs中钙清除的分子机制，我们使用单味觉细胞转录组方法寻找参与[Ca2+]c调节的分子。我们发现，Serca3是肌浆/内质网钙-ATPase(SERCA)家族中的一员，它将细胞内的钙离子隔离到内质网中，它只在甜/鲜味/苦味TRCs中表达，它依赖于细胞内钙的释放来进行信号传递。Serca3基因敲除(KO)小鼠表现出对苦味物质的厌恶行为反应和更强的味觉神经反应，但对甜味或鲜味物质没有。进一步的研究表明，SERCA2主要在表达T1R3的甜味和鲜味TRCs中表达，提示SERCA2可能补偿了突变小鼠这些TRCs中Serca3功能的丧失。我们的数据表明，SERCA家族成员在TRCs的钙清除过程中发挥着重要作用，这些蛋白的突变可能会改变人们对苦味、甜味和鲜味的感知。
The sense of taste is important for providing animals with valuable information about the qualities of food, such as nutritional or harmful nature. Mammals, including humans, can recognize at least five primary taste qualities: sweet, umami (savory), bitter, sour, and salty. Recent studies have identified molecules and mechanisms underlying the initial steps of tastant-triggered molecular events in taste bud cells, particularly the requirement of increased cytosolic free Ca2+ concentration ([Ca2+]c) for normal taste signal transduction and transmission. Little, however, is known about the mechanisms controlling the removal of elevated [Ca2+]c from the cytosol of taste receptor cells (TRCs) and how the disruption of these mechanisms affects taste perception. To investigate the molecular mechanism of Ca2+ clearance in TRCs, we sought the molecules involved in [Ca2+]c regulation using a single-taste-cell transcriptome approach. We found that Serca3, a member of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) family that sequesters cytosolic Ca2+ into endoplasmic reticulum, is exclusively expressed in sweet/umami/bitter TRCs, which rely on intracellular Ca2+ release for signaling. Serca3-knockout (KO) mice displayed significantly increased aversive behavioral responses and greater gustatory nerve responses to bitter taste substances but not to sweet or umami taste substances. Further studies showed that Serca2 was mainly expressed in the T1R3-expressing sweet and umami TRCs, suggesting that the loss of function of Serca3 was possibly compensated by Serca2 in these TRCs in the mutant mice. Our data demonstrate that the SERCA family members play an important role in the Ca2+ clearance in TRCs and that mutation of these proteins may alter bitter and perhaps sweet and umami taste perception.
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