Activity-based, bioorthogonal imaging of phospholipase D reveals spatiotemporal dynamics of GPCR-Gq signaling.
Activity-based, bioorthogonal imaging of phospholipase D reveals spatiotemporal dynamics of GPCR-Gq signaling.
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磷脂酶D的基于活性的生物正交成像揭示了GPCR-Gq信号传导的时空动力学。
DOI：
10.1016/j.chembiol.2021.05.020
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发表时间：
2022-01-20
影响因子：
8.6
通讯作者：
Baskin JM
中科院分区：
文献类型：
--
作者：
Liang D;Cheloha RW;Watanabe T;Gardella TJ;Baskin JM
典型地，GPCR信号传导是瞬时的并且局限于质膜（PM）。与此不同的是，甲状旁腺激素受体（PTHR 1）刺激核内体持续的Gs信号传导。除Gs外，PTHR 1还激活Gq信号传导;然而，与PTHR 1-Gs通路相反，PTHR 1信号传导的Gq分支的时空动力学及其与Gs信号传导的关系在很大程度上仍不明确。认识到Gq信号传导的下游结果是磷脂酶D（PLD）酶的激活，我们利用PLD信号传导的基于活性的生物正交成像工具来可视化和量化PTHR 1信号传导的Gq分支。我们确定PTHR 1-Gq信号传导是短暂的，仅在PM，并被PTHR 1内吞作用拮抗。我们的数据支持Gq和Gs在PM竞争配体结合受体的模型，并且更广泛地突出了生物正交工具用于成像PLD作为探针以可视化GPCR-Gq信号传导的效用。甲状旁腺激素受体（PTHR 1）通过Gs和Gq发出信号，前者非经典地发生在核内体上。在这里，Liang等人应用生物正交方法来可视化磷脂酶D信号传导，以揭示PTHR 1-Gq信号传导是瞬时的并且仅定位于质膜。
Canonically, GPCR signaling is transient and confined to the plasma membrane (PM). Deviating from this paradigm, the parathyroid hormone receptor (PTHR1) stimulates sustained Gs signaling at endosomes. In addition to Gs, PTHR1 activates Gq signaling; yet, in contrast to the PTHR1–Gs pathway, the spatiotemporal dynamics of the Gq branch of PTHR1 signaling, and its relationship to Gs signaling, remain largely ill-defined. Recognizing that a downstream consequence of Gq signaling is the activation of phospholipase D (PLD) enzymes, we leverage activity-based, bioorthogonal imaging tools for PLD signaling to visualize and quantify the Gq branch of PTHR1 signaling. We establish that PTHR1–Gq signaling is short-lived, exclusively at the PM, and antagonized by PTHR1 endocytosis. Our data support a model wherein Gq and Gs compete for ligand-bound receptors at the PM and more broadly highlight the utility of bioorthogonal tools for imaging PLDs as probes to visualize GPCR–Gq signaling. The parathyroid hormone receptor (PTHR1) signals via both Gs and Gq, with the former occurring, non-classically, on endosomes. Here, Liang et al. apply a bioorthogonal method for visualizing phospholipase D signaling to reveal that PTHR1–Gq signaling is transient and localized exclusively at the plasma membrane.
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影响因子：
46.9
作者：
Cheloha, Ross W.;Maeda, Akira;Dean, Thomas;Gardella, Thomas J.;Gellman, Samuel H.
通讯作者：
Gellman, Samuel H.
DOI：
10.1073/pnas.1903949116
发表时间：
2019-07-30
影响因子：
11.1
作者：
Liang, Dongjun;Wu, Kane;Baskin, Jeremy M.
通讯作者：
Baskin, Jeremy M.
影响因子：
64.5
作者：
Inoue, Asuka;Raimondi, Francesco;Russell, Robert B.
通讯作者：
Russell, Robert B.
影响因子：
4
作者：
Binkowski, Brock F.;Butler, Braeden L.;Wood, Keith V.
通讯作者：
Wood, Keith V.
影响因子：
4.8
作者：
Harper, Callista B.;Martin, Sally;Meunier, Frederic A.
通讯作者：
Meunier, Frederic A.