灵长类苦味受体基因研究进展

在鲜味、甜味、苦味、咸味和酸味5种味觉形式中,苦味能避免动物摄入有毒有害物质,在动物的生存中发挥着特别重要的作用。苦味味觉的产生依赖于苦味物质与苦味受体的相互作用。苦味受体由苦味受体基因Tas2rs编码,此类基因在不同物种中数量变化较大以适应不同的需求。目前的研究在灵长类中鉴别出了若干苦味受体的配体,并发现有的苦味受体基因所经受的选择压在类群之间、基因之间甚至同一基因不同功能区之间都存在着变化。本文从苦味受体作用的多样性特点,受体与配体的对应关系、受体基因进化模式与食性之间的关系、苦味受体基因的适应性进化方面对灵长类苦味受体基因进行了综述,以期为苦味受体基因在灵长类中的深入研究提供参考。     

味觉信号的通用编码途径

味觉对于辨别甜味、苦味、酸味、咸味和鲜味 (氨基酸味 )有重要的作用。最近 ,利用遗传学、生物信息学、表达克隆等手段克隆了哺乳动物的味觉受体。甜味和鲜味是由Ｔ1Ｒ家族的三个Ｇ蛋白偶联受体介导的。苦味主要由Ｔ2Ｒ家族约 30个Ｇ蛋白偶联受体所介导。ＴＲＰＭ5是一种新近从味觉细胞中克隆的基因 ,属于ＴＲＰ钙离子通道家族。形态学研究结果表明 ,ＴＲＰＭ5与Ｔ1Ｒ或Ｔ2Ｒ受体共存 ,并且证明ＴＲＰＭ5可以被味觉受体通过磷脂酶Ｃ(ＰＬＣ)所激活。ＴＲＰＭ5或者ＰＬＣβ2基因敲除的小鼠表现出甜味、苦味和鲜味味觉缺失 ,但不影响其酸味和…     

味觉受体分子机制

味觉决定了动物的摄食,它提供了动物对食物极其重要的感觉信息。味觉可以分为甜、鲜、苦、酸和咸5种基本感觉形式。甜味受体基因有T1R2和T1R3基因,鲜味受体基因有T1R1、T1R3和mGluR4基因;苦味受体基因有T2R基因;PKD1L3和PKD2L1基因是候选的酸味受体基因;ENaC和TRPV1基因是咸味受体基因。本文综述了这五种味觉受体的基因表达、信号转导机制和分子进化机制的最新研究进展。     

味觉受体第一家族与味觉识别

哺乳动物味觉受体第一家族(taste receptor family 1 member,T1R)的发现提供了甜味与鲜味(氨基酸味)味觉识别与味觉概念一个重要的新视野。T1R包括T1R1、T1R2、T1R3三个成员。这些受体属于G蛋白偶联受体家族第3亚型,其中T1R2 T1R3以异二聚体形式共表达并参与甜味识别,而T1R1 T1R3也以异二聚体形式共表达并参与鲜味(氨基酸味)识别。对T1R的系列研究证明了味细胞对甜味和鲜味(氨基酸味)的选择性识别及其外周味觉编码的逻辑性。     

甜味机制的研究进展

甜味的感受细胞是味觉细胞,味觉细胞是个双极细胞,味觉受体是一类G蛋白偶联受体,根据甜味物质性质的不同,通过两种途径－－cAMP途径与IP3和DAG途径进行甜味转导。PKA,PKC,味素和转导素在甜味转导中发挥了不同的功能。     

甜味分子与G蛋白偶联受体Tas1R2/3的相互作用及激活机制

甜味分子与C家族G蛋白偶联受体(G protein-coupled receptor,GPCR)的成员之一甜味受体相互作用,从而激活受体并引起甜味觉的感知。本文简要总结了甜味受体(taste receptor 2 and 3,Tas1R2/3)的结构与功能、甜味分子与受体相互作用并激活受体的机制,并对甜味受体研究领域的发展前景进行了展望。甜味分子与受体相互作用机制的阐明对于理解甜味觉的产生与GPCR的结构与功能具有重要的意义。此外,甜味受体结构与功能的研究可为有针对性地设计新型甜味化合物提供理论基础。     

肾上腺素受体对心血管细胞生长和凋亡的影响

肾上腺素受体广泛存在于心血管系统。心肌肥厚,心衰,心动粥样硬化等病理过程往往伴有心血管细胞的异常生长和凋亡,研究表明儿茶酚胺可经不同的肾上腺素受体通过不同的信号转导途径,如α－肾上腺素受体主要通过磷酯磷Ｃ／蛋白激酶Ｃ途径,β－肾上腺素受体则主要通过蛋白激酶Ａ／ｃＡＭＰ途径或激活钙通道对心肌细胞,血管平滑肌细胞,内皮细胞等的生长与凋亡产生影响,探讨肾上腺素受体对心血管细胞生长和凋亡的作用机制,具有重     

水稻中受体激酶的系统树分析

植物受体激酶(RLKs)在植物细胞内的反应中发挥着重要作用。为了比较拟南芥(Arabidopsis thaliana L.)和水稻(Oryza sativa L.)中受体激酶的进化关系,作者通过对北京华大基因研究中心(BGI)的籼稻蛋白质数据库进行BLASTP搜索,找到267个受体激酶类似基因,根据它们的胞外结构域可以将这些基因分为不同的类型。与拟南芥中受体激酶的系统树比较分析表明,不同类型的受体激酶具有不同的序列保守性,说明在植物进化过程中,不同类型的受体激酶具有不同的进化关系。水稻受体激酶与拟南芥受体激酶BRI1的多序列匹配结果也表明二者可能具有不同的磷酸化位点。     

水稻中受体激酶的系统树分析

植物受体激酶(RLKs)在植物细胞内的反应中发挥着重要作用.为了比较拟南芥(Arabidopsis thaliana L.)和水稻(Oryza sativa L.)中受体激酶的进化关系,作者通过对北京华大基因研究中心(BGI)的籼稻蛋白质数据库进行BLASTP搜索,找到267个受体激酶类似基因,根据它们的胞外结构域可以将这些基因分为不同的类型.与拟南芥中受体激酶的系统树比较分析表明,不同类型的受体激酶具有不同的序列保守性,说明在植物进化过程中,不同类型的受体激酶具有不同的进化关系.水稻受体激酶与拟南芥受体激酶BRI1的多序列匹配结果也表明二者可能具有不同的磷酸化位点.     

油菜素甾醇类信号转导受体研究进展

在植物和动物的生长发育过程中,甾醇和肽类激素被广泛地作为信号转导分子来使用。在植物中,油菜素甾醇类（BRs）信号由细胞表面受体激酶BRI1感知,该受体与动物的甾醇受体有明显的区别。对BR信号转导途径中组分的鉴定表明,该途径与其地动物和植物信号转导途径具有类似性。近来的研究证实番茄BRI1（tBRIl）能感知BR和肽类激素系统素。于是,关于受体一配体特异性的分子机制及进化的问题便产生了。本文就目前关于BRs信号转导中受体的研究进展作一综述。     

Molecular mechanisms underlying the reception and transmission of sour taste information

Taste enables organisms to determine the properties of ingested substances by conveying information regarding the five basic taste modalities: sweet, salty, sour, bitter, and umami. The sweet, salty, and umami taste modalities convey the carbohydrate, electrolyte, and glutamate content of food, indicating its desirability and stimulating appetitive responses. The sour and bitter modalities convey the acidity of food and the presence of potential toxins, respectively, stimulating aversive responses to such tastes. In recent years, the receptors mediating sweet, bitter, and umami tastes have been identified as members of the T1R and T2R G-protein-coupled receptor families; however, the molecular mechanisms underlying sour taste detection have yet to be clearly elucidated. This review covers the molecular mechanisms proposed to mediate the detection and transmission of sour stimuli, focusing on polycystic kidney disease 1-like 3 (Pkd1l3), Pkd2l1, and carbonic anhydrase 4 (Car4).     

鲜味受体研究进展

味觉对于生命具有重要作用,在一定程度上确定了人类对事物的选择。味觉由甜、咸、苦、酸和鲜等5种基本味道组成,味觉的感知是通过存在于舌上味觉表面的特异性受体来实现的,大多数味觉受体都属于G蛋白偶联受体家族。近几年的研究揭示了感知鲜味的2类这样的受体,鲜觉受体的阐明使人们对味觉的理解有了较为全面的认识。     

The good taste of peptides

The taste of peptides is seldom one of the most relevant issues when one considers the many important biological functions of this class of molecules. However, peptides generally do have a taste, covering essentially the entire range of established taste modalities: sweet, bitter, umami, sour and salty. The last two modalities cannot be attributed to peptides as such because they are due to the presence of charged terminals and/or charged side chains, thus reflecting only the zwitterionic nature of these compounds and/or the nature of some side chains but not the electronic and/or conformational features of a specific peptide. The other three tastes, that is, sweet, umami and bitter, are represented by different families of peptides. This review describes the main peptides with a sweet, umami or bitter taste and their relationship with food acceptance or rejection. Particular emphasis will be given to the sweet taste modality, owing to the practical and scientific relevance of aspartame, the well‐known sweetener, and to the theoretical importance of sweet proteins, the most potent peptide sweet molecules. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Trpm5 null mice respond to bitter, sweet, and umami compounds

Trpm5 is a calcium-activated cation channel expressed selectively in taste receptor cells. A previous study reported that mice with an internal deletion of Trpm5, lacking exons 15-19 encoding transmembrane segments 1-5, showed no taste-mediated responses to bitter, sweet, and umami compounds. We independently generated knockout mice null for Trpm5 protein expression due to deletion of Trpm5's promoter region and exons 1-4 (including the translation start site). We examined the taste-mediated responses of Trpm5 null mice and wild-type (WT) mice using three procedures: gustatory nerve recording [chorda tympani (CT) and glossopharyngeal (NG) nerves], initial lick responses, and 24-h two-bottle preference tests. With bitter compounds, the Trpm5 null mice showed reduced, but not abolished, avoidance (as indicated by licking responses and preference ratios higher than those of WT), a normal CT response, and a greatly diminished NG response. With sweet compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, and absent or greatly reduced nerve responses. With umami compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, a normal NG response, and a greatly diminished CT response. Our results demonstrate that the consequences of eliminating Trmp5 expression vary depending upon the taste quality and the lingual taste field examined. Thus, while Trpm5 is an important factor in many taste responses, its absence does not eliminate all taste responses. We conclude that Trpm5-dependent and Trpm5-independent pathways underlie bitter, sweet, and umami tastes.     

Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes

Taste reception is fundamental to diet selection in many animals. The genetic basis underlying the evolution and diversity of taste reception, however, is not well understood. Recent discoveries of T1R sweet/umami receptor genes and T2R bitter receptor genes in humans and mice provided an opportunity to address this question. Here, we report the identification of 20 putatively functional T1R genes and 167 T2R genes from the genome sequences of nine vertebrates, including three fishes, one amphibian, one bird, and four mammals. Our comparative genomic analysis shows that orthologous T1R sequences are relatively conserved in evolution and that the T1R gene repertoire remains virtually constant in size across most vertebrates, except for the loss of the T1R2 sweet receptor gene in the sweet-insensitive chicken and the absence of all T1R genes in the tongueless western clawed frog. In contrast, orthologous T2R sequences are more variable, and the T2R repertoire diverges tremendously among species, from only three functional genes in the chicken to 49 in the frog. These evolutionary patterns suggest the relative constancy in the number and type of sweet and umami tastants encountered by various vertebrates or low binding specificities of T1Rs but a large variation in the number and type of bitter compounds detected by different species. Although the rate of gene duplication is much lower in T1Rs than in T2Rs, signals of positive selection are detected during the functional divergences of paralogous T1Rs, as was previously found among paralogous T2Rs. Thus, functional divergence and specialization of taste receptors generally occurred via adaptive evolution.     

Evolutionary insights into umami,sweet, and bitter taste receptors in amphibians

Umami and sweet sensations provide animals with important dietary information for detecting and consuming nutrients, whereas bitter sensation helps animals avoid potentially toxic or harmful substances. Enormous progress has been made toward animal sweet/umami taste receptor (Tas1r) and bitter taste receptor (Tas2r). However, information about amphibians is mainly scarce. This study attempted to delineate the repertoire of Tas1r/Tas2r genes by searching for currently available genome sequences in 14 amphibian species. This study identified 16 Tas1r1, 9 Tas1r2, and 9 Tas1r3 genes to be intact and another 17 Tas1r genes to be pseudogenes or absent in the 14 amphibians. According to the functional prediction of Tas1r genes, two species have lost sweet sensation and seven species have lost both umami and sweet sensations. Anurans possessed a large number of intact Tas2rs, ranging from 39 to 178. In contrast, caecilians possessed a contractive bitter taste repertoire, ranging from 4 to 19. Phylogenetic and reconciling analysis revealed that the repertoire of amphibian Tas1rs and Tas2rs was shaped by massive gene duplications and losses. No correlation was found between feeding preferences and the evolution of Tas1rs in amphibians. However, the expansion of Tas2rs may help amphibians adapt to both aquatic and terrestrial habitats. Bitter detection may have played an important role in the evolutionary adaptation of vertebrates in the transition from water to land.     

Expression of gustducin overlaps with that of type III IP3 receptor in taste buds of the rat soft palate

Type III IP3 receptor (IP3R3) is one of the common critical calcium-signaling molecules for sweet, umami, and bitter signal transduction in taste cells, and the total IP3R3-expressing cell population represents all cells mediating these taste modalities in the taste buds. Although gustducin, a taste cell-specific G-protein, is also involved in sweet, umami, and bitter signal transduction, the expression of gustducin is restricted to different subsets of IP3R3-expressing cells by location in the tongue. Based on the expression patterns of gustducin and taste receptors in the tongue, the function of gustducin has been implicated primarily in bitter taste in the circumvallate (CV) papillae and in sweet taste in the fungiform (FF) papillae. However, in the soft palate (SP), the expression pattern of gustducin remains unclear and little is known about its function. In the present paper, the expression patterns of gustducin and IP3R3 in taste buds of the SP and tongue papillae in the rat were examined by double-color whole-mount immunohistochemistry. Gustducin was expressed in almost all (96.7%) IP3R3-expressing cells in taste buds of the SP, whereas gustducin-positive cells were 42.4% and 60.1% of IP3R3-expressing cells in FF and CV, respectively. Our data suggest that gustducin is involved in signal transduction of all the tastes of sweet, umami, and bitter in the SP, in contrast to its limited function in the tongue.     

Genetic tracing of the neural pathway for bitter taste in t2r5-WGA transgenic mice

To visualize the neural pathways originating from bitter taste receptor cells (TRCs), we generated transgenic mice expressing the transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse T2R5 gene promoter/enhancer (t2r5-WGA mice). WGA mRNA was specifically expressed in bitter TRCs. The WGA protein was detected in bitter TRCs and nerve processes in taste buds, but not in sweet, umami, or sour TRCs. The WGA protein was transferred to a subset of sensory neurons in the geniculate and nodose/petrosal ganglia. These results suggest that bitter TRCs, which are devoid of synaptic structures, are innervated by gustatory neurons and that bitter sensory information is directly transmitted to specific gustatory neurons. The t2r5-WGA mice provide a useful tool for identifying gustatory relay neurons in the peripheral sensory ganglia responsible for aversive sensations.     

Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells

Taste receptors cells are responsible for detecting a wide variety of chemical stimuli. Several molecules including both G protein coupled receptors and ion channels have been shown to be involved in the detection and transduction of tastants. We report on the expression of two members of the transient receptor potential (TRP) family of ion channels, PKD1L3 and PKD2L1, in taste receptor cells. Both of these channels belong to the larger polycystic kidney disease (PKD or TRPP) subfamily of TRP channels, members of which have been demonstrated to be non-selective cation channels and permeable to both Na(+) and Ca(2+). Pkd1l3 and Pkd2l1 are co-expressed in a select subset of taste receptor cells and therefore may, like other PKD channels, function as a heteromer. We found the taste receptor cells expressing Pkd1l3 and Pkd2l1 to be distinct from those that express components of sweet, bitter and umami signal transduction pathways. These results provide the first evidence for a role of TRPP channels in taste receptor cell function.