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光诱导的受体约束驱动配体非依赖性 GPCR 信号转导。

Photoinduced receptor confinement drives ligand-independent GPCR signaling.

机构信息

Institute of Biochemistry, Biocenter, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany.

Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, 04109 Leipzig, Germany.

出版信息

Science. 2021 Mar 26;371(6536). doi: 10.1126/science.abb7657. Epub 2021 Feb 25.

DOI:10.1126/science.abb7657
PMID:33632896
Abstract

Cell-cell communication relies on the assembly of receptor-ligand complexes at the plasma membrane. The spatiotemporal receptor organization has a pivotal role in evoking cellular responses. We studied the clustering of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) and established a photoinstructive matrix with ultrasmall lock-and-key interaction pairs to control lateral membrane organization of hormone neuropeptide Y receptors in living cells by light. Within seconds, receptor clustering was modulated in size, location, and density. After in situ confinement, changes in cellular morphology, motility, and calcium signaling revealed ligand-independent receptor activation. This approach may enhance the exploration of mechanisms in cell signaling and mechanotransduction.

摘要

细胞间通讯依赖于质膜上受体-配体复合物的组装。时空受体组织在引发细胞反应中起着关键作用。我们研究了异三聚体鸟苷酸结合蛋白(G 蛋白)-偶联受体(GPCR)的聚类,并建立了一个具有超小锁和键相互作用对的光指令性矩阵,通过光来控制激素神经肽 Y 受体在活细胞中的侧向膜组织。在几秒钟内,受体聚类的大小、位置和密度发生了变化。在原位限制之后,细胞形态、运动和钙信号的变化揭示了配体非依赖性受体激活。这种方法可能有助于探索细胞信号转导和力学转导中的机制。

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