Sensory perception of sweet, bitter, and umami (glutamate) taste

Taste receptors for bitter compounds, sweet compounds, and umami compounds (L-glutamate in humans, several amino acids in mice) are G protein-coupled receptors located in type II taste bud cells that signal through a common downstream pathway (reviewed in Margolskee 2002, Kinnamon 2009, Kurihara 2015, Roper and Chauhari et al. 2017, Kinnamon and Finger 2019, Servant et al. 2020). Umami ("savoury", L-glutamate) taste receptors are heterodimers of the plasma membrane proteins TAS1R1 and TAS1R3. TAS1R1:TAS1R3 heterodimers also bind 5' nucleotides such as 5' IMP which synergistically augment umami taste. The glutamate receptors GRM1 (mGluR1) and GRM4 (mGluR4) act in an alternative pathway for sensing glutamate in taste cells (reviewed in Chaudhari et al. 2009). Sweet taste receptors are heterodimers of the plasma membrane proteins TAS1R2 and TAS1R3 (reviewed in Yang et al. 2021). The glucose transporters SGLT1 and GLUT4 are expressed in type II taste cells and may provide an alternative pathway for sensing glucose (reviewed in von Molitor et al. 2020). Bitter receptors are a large family of monomeric plasma membrane proteins, the TAS2R proteins.<br> TAS1R-containing sweet and umami receptors and TAS2R bitter receptors are each physically associated with a particular heterotrimeric G protein complex, the gustducin complex, containing GNAT3 (gustducin), GNB1 or GNB3, and GNG13. Upon binding an agonist ligand, the receptor activates the alpha subunit, GNAT3, to exchange GDP for GTP, which results in a conformational change in GNAT3 that causes the receptor-gustducin complex to dissociate, yielding GNAT3:GTP, GNB1,3:GNG13, and the receptor:ligand. The GNB1,3:GNG13 complex binds and activates Phospholipase C beta-2 (PLCB2), which then hydrolyzes phosphoinositol 4,5-bisphosphate (PI(4,5)P2) to yield diacylglycerol and inositol 1,4,5-trisphosphate (I(1,4,5)P3). I(1,4,5)P3 binds and activates the calcium channel IP3-gated Ca-channel type 3 (ITPR3) and ITPR3 then releases calcium ions from the endoplasmic reticulum into the cytosol. The increased cytosolic calcium activates the TRPM5 cation channels, which then transport sodium ions along the concentration gradient from the extracellular region to the cytosol (reviewed in Aroke et al. 2020). The depolarization activates SCN2A, SCN3A, and SCN9A channels, which transport further sodium ions from the extracellular region to the cytosol. The depolarization of the plasma membrane opens CALHM1:CALHM3 channels, which transport ATP, a neurotransmitter in the olfactory system, from the cytosol to the extracellular region.<br>Taste receptors were initially discovered in taste buds of the tongue and have now been found in several other tissues including nasal epithelium (Barnham et al. 2015, inferred from rodent homologs in Tizzano et al. 2011), the respiratory system, pancreatic islet cells, sperm (Governini et al. 2020), leukocytes (Malki et al. 2015), and enteroendocrine cells of the gut (inferred from rat and mouse homologs in Wu et al. 2002).

苦味、甜味以及谷氨酸（人类中的L-谷氨酸，小鼠中的多种氨基酸）等鲜味化合物的味觉受体均为G蛋白偶联受体，它们位于II型味蕾细胞中，并通过共同的下游信号通路进行信号传递（参见Margolskee 2002年、Kinnamon 2009年、Kurihara 2015年、Roper和Chauhari等2017年、Kinnamon和Finger 2019年、Servant等2020年的综述）。鲜味（即“滋味”，L-谷氨酸）味觉受体是由细胞膜蛋白TAS1R1和TAS1R3组成的异源二聚体。TAS1R1:TAS1R3异源二聚体还能够结合如5' IMP等5'核苷酸，通过协同作用增强鲜味。谷氨酸受体GRM1（mGluR1）和GRM4（mGluR4）在味觉细胞中通过替代途径感知谷氨酸（参见Chaudhari等2009年的综述）。甜味受体是由细胞膜蛋白TAS1R2和TAS1R3组成的异源二聚体（参见Yang等2021年的综述）。葡萄糖转运蛋白SGLT1和GLUT4在II型味觉细胞中表达，可能为感知葡萄糖提供替代途径（参见von Molitor等2020年的综述）。苦味受体是一大家族的单体细胞膜蛋白，即TAS2R蛋白。包含GNAT3（味觉素）、GNB1或GNB3、GNG13的特定异源三聚体G蛋白复合体（味觉素复合体）与含有TAS1R的甜味和鲜味受体以及TAS2R苦味受体在物理上相联系。当受体与激动剂配体结合时，会激活α亚基GNAT3，使其GDP交换为GTP，导致GNAT3构象改变，从而使受体-味觉素复合体解离，生成GNAT3:GTP、GNB1,3:GNG13和受体-配体复合物。GNB1,3:GNG13复合物结合并激活磷脂酰肌醇特异性磷脂酶C beta-2（PLCB2），然后PLCB2水解磷脂酰肌醇4,5-二磷酸（PI(4,5)P2）生成二酰甘油和肌醇1,4,5-三磷酸（I(1,4,5)P3)。I(1,4,5)P3结合并激活IP3门控的钙通道3型（ITPR3），随后ITPR3从内质网释放钙离子到细胞质中。细胞质中钙离子的增加激活了TRPM5阳离子通道，这些通道随后沿着浓度梯度将钠离子从细胞外区域转运到细胞质中（参见Aroke等2020年的综述）。去极化激活了SCN2A、SCN3A和SCN9A通道，这些通道将更多的钠离子从细胞外区域转运到细胞质中。细胞膜的去极化打开CALHM1:CALHM3通道，这些通道将作为嗅觉系统神经递质的ATP从细胞质转运到细胞外区域。<br>味觉受体最初在舌的味蕾中被发现，现在已经在包括鼻上皮（Barnham等2015年，根据Tizzano等2011年的啮齿动物同源物推断）、呼吸系统、胰腺胰岛细胞、精子（Governini等2020年）、白细胞（Malki等2015年）和肠道肠内分泌细胞（根据Wu等2002年的大鼠和小鼠同源物推断）在内的多种组织中找到。