Marullo Stefano, Doly Stephane, Saha Kusumika, Enslen Hervé, Scott Mark G H, Coureuil Mathieu
Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR 8104, 75014 Paris, France.
Université Clermont Auvergne, INSERM, NEURO-DOL, 63000 Clermont-Ferrand, France.
ACS Pharmacol Transl Sci. 2020 Feb 21;3(2):171-178. doi: 10.1021/acsptsci.9b00106. eCollection 2020 Apr 10.
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 β-adrenergic receptor by a pathogen revealed that traction forces directly exerted on the N-terminus of the receptor via -glycan chains activate specific signaling pathways. These findings open new perspectives in GPCR biology and pharmacology since most GPCRs express -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.
细胞对化学刺激敏感，化学刺激通过特定受体的激活转化为细胞内生化信号。机械刺激也可通过激活各种机械传感器诱导生化反应。尽管G蛋白偶联受体（GPCRs）主要因其化学传感功能而受到重视，但它们可能参与机械转导。它们通过对机械刺激作出反应而分泌的化合物的旁分泌释放而间接激活，但它们也可能额外表现为直接受机械力刺激的机械传感器。尽管多项研究与后一种假设一致，但直到最近，GPCRs潜在直接机械激活的分子机制仍不清楚。特别是，对一种病原体激活儿茶酚胺β-肾上腺素能受体的研究表明，通过聚糖链直接施加在受体N端的牵引力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视角，因为大多数GPCRs在其N端表达聚糖链，在细胞间机械信号传导的背景下，这些聚糖链可能同样参与与细胞表面聚糖特异性凝集素的相互作用。
