Biased sweet taste signaling pathways in mice and humans

小鼠和人类中偏向的甜味信号通路

基本信息

  • 批准号:
    10456040
  • 负责人:
  • 金额:
    $ 13.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-08-05 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

The obesity epidemic has reached alarming proportions in many parts of the world, fueled by the over consumption of calorie-rich foods, primarily sugars in the form of sugar-sweetened beverages and other sweet foods. Hence, novel strategies are needed to prevent excessive sugar consumption and to promote a healthy diet. Non-caloric sweeteners have been used for several decades to replace sugar-derived calories. However, their health benefits have been questioned and their taste profile is inferior to sugars. Therefore, there is a need to develop novel healthy and tasty non-caloric sweeteners. The sweet taste receptor - a heterodimeric G-protein coupled receptor (GPCR) formed by the TAS1R2 and TAS1R3 subunits - is the primary receptor for sugars and non-caloric sweeteners. Studies to date have focused on the G-protein mediated pathway as the primary mechanism for transduction of sweet taste signaling downstream of the sweet taste receptor. However, it is now well known that the arrestins, adaptor proteins first identified as mediators of GPCR- desensitization, can transduce signals down stream of GPCRs on their own. The G-protein and arrestin pathways engage different downstream signaling partners and consequently, have different physiological effects. An exciting development in pharmacology is the discovery that some GPCR ligands differentially engage the G-protein and arrestin pathways, although they bind to the same receptor. Such biased ligands are exciting drug candidates. Using single-cell RNASeq, we showed that Arrb1 is the sole arrestin expressed in sweet taste receptor expressing cells. We propose to identify the role of arrestin signaling in sweet taste using conditional knockout (CKO) mice models and taste organoids cultured from this strain. We will confirm the specific expression of Arrb1 in sweet taste cells using in situ hybridization and immunohistochemistry and will compare the behavioral and taste nerve responses of Arrb1CKO and control mice to sweet and other control taste stimuli. The kinetics of arrestin binding to the sweet taste receptor, sweet taste adaptation, and arrestin signaling will be studied in taste organoids using microscopic and other assays (Specific Aim 1). Unfortunately, such mechanistic studies are not possible in humans, as human taste stem cells have not been identified. We will use cutting-edge spatial transcriptomics of human and mouse taste papillae and compare this to existing droplet-based scRNASeq data from mouse cells, to identify human taste cell types including stem cells and the growth factors required for regeneration of taste cells (Specific Aim 2). Data from this study will enable the development of tools and strategies to manipulate sweet taste signaling.
在世界上许多地方,肥胖的流行已经达到了令人担忧的程度,这是由过度消费所推动的

项目成果

期刊论文数量(0)
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Sunil Kumar Sukumaran其他文献

Sunil Kumar Sukumaran的其他文献

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{{ truncateString('Sunil Kumar Sukumaran', 18)}}的其他基金

Mucosal Immune Surveillance at the Taste Papillae
味乳头的粘膜免疫监视
  • 批准号:
    10576135
  • 财政年份:
    2022
  • 资助金额:
    $ 13.26万
  • 项目类别:
Mucosal Immune Surveillance at the Taste Papillae
味乳头的粘膜免疫监视
  • 批准号:
    10693341
  • 财政年份:
    2022
  • 资助金额:
    $ 13.26万
  • 项目类别:
Biased sweet taste signaling pathways in mice and humans
小鼠和人类中偏向的甜味信号通路
  • 批准号:
    10867691
  • 财政年份:
    2022
  • 资助金额:
    $ 13.26万
  • 项目类别:
Biased sweet taste signaling pathways in mice and humans
小鼠和人类中偏向的甜味信号通路
  • 批准号:
    10215441
  • 财政年份:
    2014
  • 资助金额:
    $ 13.26万
  • 项目类别:
Biased sweet taste signaling pathways in mice and humans
小鼠和人类中偏向的甜味信号通路
  • 批准号:
    10192528
  • 财政年份:
  • 资助金额:
    $ 13.26万
  • 项目类别:
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