研究人员揭示了异三聚鸟嘌呤核苷酸结合蛋白(G蛋白)偶联受体(GPCR)的成簇行为,并建立了具有超小型锁-钥相互作用配对的光引导型基质,从而能够通过光控制活细胞中激素神经肽Y2受体的侧向膜改变。在几秒钟内,受体簇的大小、位置和密度得到调节。
在原位限制后,细胞形态、运动性和钙信号的变化揭示了配体非依赖的受体激活。该方法可以增强对细胞信号传导和机械转导机制的探索。
据悉,细胞之间的通讯依赖于质膜上受体-配体复合物的组装。时空受体组织在引起细胞反应中起关键作用。
附:英文原文
Title: Photo-induced receptor confinement drives ligand-independent GPCR signaling
Author: M. Florencia Sánchez, Sylvia Els-Heindl, Annette G. Beck-Sickinger, Ralph Wieneke, Robert Tampé
Issue&Volume: 2021/02/25
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 photo-instructive matrix with ultra-small lock-and-key interaction pairs to control lateral membrane organization of hormone neuropeptide Y2 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 exploration of mechanisms in cell signaling and mechanotransduction.
DOI: 10.1126/science.abb7657
Source: https://science.sciencemag.org/content/early/2021/02/24/science.abb7657