甜味、苦味和味素（谷氨酸）感觉的感知
中文名称
通路描述
苦味化合物、甜味化合物和味素化合物（人类为 L-谷氨酸，小鼠为几种氨基酸）的味觉受体位于 II 型味细胞中的 G 蛋白偶联受体，通过共同的下游信号通路进行信号转导（综述 Margolskee 2002, Kinnamon 2009, Kurihara 2015, Roper and Chauhari 等人 2017, Kinnamon and Finger 2019, Servant 等人 2020）。味素（“鲜味”，L-谷氨酸）味觉受体是 TAS1R1 和 TAS1R3 血浆膜蛋白异二聚体。TAS1R1:TAS1R3 异二聚体还结合 5'核苷酸如 5'-IMP，协同增强味素感觉。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（综述 Chaudhari 等人 2009）。甜味受体是 TAS1R2 和 TAS1R3 血浆膜蛋白异二聚体（综述 Yang 等人 2021）。葡萄糖转运蛋白 SGLT1 和 GLUT4 表达于 II 型味细胞中，可能提供感知葡萄糖的替代途径（综述 von Molitor 等人 2020）。苦味受体是一类单体血浆膜蛋白，即 TAS2R 蛋白。TAS1R 含甜味和味素受体与 TAS2R 苦味受体分别与特定的三聚体 G 蛋白复合物物理结合，即味ducin 复合物，包含 GNAT3（味ducin）、GNB1 或 GNB3 以及 GNG13。当受体结合激动剂配体时，受体激活α亚基 GNAT3，使其交换 GDP 为 GTP，导致 GNAT3 构象变化，使受体 -味ducin 复合物解离，产生 GNAT3:GTP, GNB1,3:GNG13 和受体：配体。GNB1,3:GNG13 复合物结合并激活磷脂酶 Cβ-2（PLCB2），后者水解磷脂酰肌醇 4,5-二磷酸（PI(4,5)P2）产生二酰甘油和肌醇 1,4,5-三磷酸（I(1,4,5)P3）。I(1,4,5)P3 结合并激活钙通道 IP3 门控 Ca 通道类型 3（ITPR3）和 ITPR3，然后从内质网释放钙离子入细胞质。增加的细胞质钙激活 TRPM5 阳离子通道，随后沿浓度梯度将钠离子从细胞外区域运输到细胞质（综述 Aroke 等人 2020）。膜电位去极化激活 SCN2A、SCN3A 和 SCN9A 通道，进一步将钠离子从细胞外区域运输到细胞质。膜电位去极化打开 CALHM1:CALHM3 通道，将 ATP（嗅觉系统中的神经递质）从细胞质运输到细胞外区域。味觉受体最初在舌头的味觉细胞中被发现，现在也在其他组织中发现，包括鼻上皮（Barnham 等人 2015，基于小鼠同源物在 Tizzano 等人 2011 中的推断）、呼吸系统、胰腺胰岛细胞、精子（Governini 等人 2020）、白细胞（Malki 等人 2015）和肠道的肠内分泌细胞（基于大鼠和小鼠同源物在 Wu 等人 2002 中的推断）。
英文描述
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.
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.
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).
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.
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).
所含基因
41 个基因