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EJE AWARD 2020: Signalling by G protein-coupled receptors: why space and time matter.

EJE奖2020: g蛋白偶联受体的信号传导: 为什么空间和时间重要。

  • 影响因子:5.04
  • DOI:10.1530/EJE-20-0890
  • 作者列表:"Calebiro D
  • 发表时间:2021-02-01
Abstract

:G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and major drug targets. They play a fundamental role in the endocrine system, where they mediate the effects of several hormones and neurotransmitters. As a result, alterations of GPCR signalling are a major cause of endocrine disorders such as congenital hypothyroidism or Cushing's syndrome. My group develops innovative optical methods such as fluorescence resonance energy transfer (FRET) and single-molecule microscopy, which allow us to investigate GPCR signalling in living cells with unprecedented spatiotemporal resolution. Using this innovative approach, we have contributed to elucidate some long-debated questions about the mechanisms of GPCR signalling and their involvement in human disease. Among other findings, these studies have led to the unexpected discovery that GPCRs are not only signalling at the cell surface, as previously assumed, but also at various intracellular sites. This has important implications to understand how hormones and neurotransmitters produce specific responses in our cells and might pave the way to innovative treatments for common diseases like diabetes or heart failure.

摘要

: g蛋白偶联受体 (gpcr) 是最大的膜受体家族和主要的药物靶标。它们在内分泌系统中起着基本作用,在内分泌系统中它们介导几种激素和神经递质的作用。因此,GPCR信号的改变是内分泌紊乱如先天性甲状腺功能减退症或库欣综合征的主要原因。我的团队开发了创新的光学方法,如荧光共振能量转移 (FRET) 和单分子显微镜,这使我们能够以前所未有的时空分辨率研究活细胞中的GPCR信号传导。使用这种创新方法,我们有助于阐明一些关于GPCR信号传导机制及其参与人类疾病的长期争论的问题。在其他发现中,这些研究导致了出乎意料的发现,即gpcr不仅如先前假设的那样在细胞表面发出信号,而且在各种细胞内位点也发出信号。这对于了解激素和神经递质如何在我们的细胞中产生特定反应具有重要意义,并可能为糖尿病或心力衰竭等常见疾病的创新治疗铺平道路。

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