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Mechanical GPCR Activation by Traction Forces Exerted on Receptor N-Glycans.
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-02-21 , DOI: 10.1021/acsptsci.9b00106 Stefano Marullo 1 , Stephane Doly 2 , Kusumika Saha 1 , Hervé Enslen 1 , Mark G H Scott 1 , Mathieu Coureuil 3
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-02-21 , DOI: 10.1021/acsptsci.9b00106 Stefano Marullo 1 , Stephane Doly 2 , Kusumika Saha 1 , Hervé Enslen 1 , Mark G H Scott 1 , Mathieu Coureuil 3
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Cells are sensitive to chemical stimulation which is converted into intracellular biochemical signals by the activation of specific receptors. Mechanical stimulations can also induce biochemical responses via the activation of various mechano-sensors. Although principally appreciated for their chemosensory function, G-protein-coupled receptors (GPCRs) may participate in mechano-transduction. They are indirectly activated by the paracrine release of chemical compounds secreted in response to mechanical stimuli, but they might additionally behave as mechano-sensors that are directly stimulated by mechanical forces. Although several studies are consistent with this latter hypothesis, the molecular mechanisms of a potential direct mechanical activation of GPCRs have remained elusive until recently. In particular, investigating the activation of the catecholamine β2-adrenergic receptor by a pathogen revealed that traction forces directly exerted on the N-terminus of the receptor via N-glycan chains activate specific signaling pathways. These findings open new perspectives in GPCR biology and pharmacology since most GPCRs express N-glycan chains in their N-terminus, which might similarly be involved in the interaction with cell-surface glycan-specific lectins in the context of cell-to-cell mechanical signaling.
中文翻译：
通过在受体N-聚糖上施加的牵引力进行机械GPCR活化。
细胞对化学刺激敏感，化学刺激通过特定受体的激活而转化为细胞内生化信号。机械刺激还可以通过激活各种机械传感器来诱导生化反应。尽管主要因其化学感应功能而受到赞赏，但G蛋白偶联受体（GPCR）可能参与机械转导。它们通过旁分泌释放响应机械刺激而分泌的化学化合物而间接激活，但它们可能还充当机械传感器，直接受机械力刺激。尽管有几项研究与后一种假设一致，但直到最近，潜在的直接机械激活GPCR的分子机制仍然难以捉摸。尤其是，对病原体对儿茶酚胺β2-肾上腺素能受体的激活进行的研究表明，牵引力通过N-聚糖链直接作用于受体的N-末端上，从而激活了特定的信号通路。这些发现为GPCR生物学和药理学开辟了新的前景，因为大多数GPCR在其N末端表达N-聚糖链，在细胞间机械结合的情况下，它们可能类似地参与与细胞表面聚糖特异性凝集素的相互作用。信号。
更新日期：2020-02-21
中文翻译：
通过在受体N-聚糖上施加的牵引力进行机械GPCR活化。
细胞对化学刺激敏感，化学刺激通过特定受体的激活而转化为细胞内生化信号。机械刺激还可以通过激活各种机械传感器来诱导生化反应。尽管主要因其化学感应功能而受到赞赏，但G蛋白偶联受体（GPCR）可能参与机械转导。它们通过旁分泌释放响应机械刺激而分泌的化学化合物而间接激活，但它们可能还充当机械传感器，直接受机械力刺激。尽管有几项研究与后一种假设一致，但直到最近，潜在的直接机械激活GPCR的分子机制仍然难以捉摸。尤其是，对病原体对儿茶酚胺β2-肾上腺素能受体的激活进行的研究表明，牵引力通过N-聚糖链直接作用于受体的N-末端上，从而激活了特定的信号通路。这些发现为GPCR生物学和药理学开辟了新的前景，因为大多数GPCR在其N末端表达N-聚糖链，在细胞间机械结合的情况下，它们可能类似地参与与细胞表面聚糖特异性凝集素的相互作用。信号。
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