{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huo Y"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["9843"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12595035"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["The heterodimeric GABA<sub>B</sub> receptor, composed of GB1 and GB2 subunits, is a metabotropic G protein-coupled receptor (GPCR) activated by the neurotransmitter GABA. GABA binds to the extracellular domain of GB1 to activate G proteins through GB2. Here we show that GABA<sub>B</sub> receptors can be activated by mechanical forces, such as traction force and shear stress, in a GABA-independent manner. This GABA-independent mechano-activation of GABA<sub>B</sub> receptor is mediated by a direct interaction between integrins and the extracellular domain of GB1, indicating that GABA<sub>B</sub> receptor and integrin form a mechano-transduction complex. Mechanistically, shear stress promotes the binding of integrin to GB1 and induces an allosteric re-arrangement of GABA<sub>B</sub> receptor transmembrane domains towards an active conformation, culminating in receptor activation. Furthermore, we demonstrate that shear stress-induced GABA<sub>B</sub> receptor activation plays a crucial role in astrocyte remodeling. These findings reveal a role of GABA<sub>B</sub> receptor in mechano-transduction, uncovering a ligand-independent activation mechanism for GPCRs."],"journal":["Nature communications"],"pubmed_title":["GABA-independent activation of GABA&lt;sub&gt;B&lt;/sub&gt; receptor by mechanical forces."],"pmcid":["PMC12595035"],"funding_grant_id":["32271198","32421003","32330049","82320108021"],"pubmed_authors":["He F","Zhang F","Liu J","Shawn Xu XZ","Xu C","Shen C","Zhou Y","Yang F","Liu Y","Song M","Huo Y","Meng J","Rondard P","Lin L"],"additional_accession":[]},"is_claimable":false,"name":"GABA-independent activation of GABA&lt;sub&gt;B&lt;/sub&gt; receptor by mechanical forces.","description":"The heterodimeric GABA<sub>B</sub> receptor, composed of GB1 and GB2 subunits, is a metabotropic G protein-coupled receptor (GPCR) activated by the neurotransmitter GABA. GABA binds to the extracellular domain of GB1 to activate G proteins through GB2. Here we show that GABA<sub>B</sub> receptors can be activated by mechanical forces, such as traction force and shear stress, in a GABA-independent manner. This GABA-independent mechano-activation of GABA<sub>B</sub> receptor is mediated by a direct interaction between integrins and the extracellular domain of GB1, indicating that GABA<sub>B</sub> receptor and integrin form a mechano-transduction complex. Mechanistically, shear stress promotes the binding of integrin to GB1 and induces an allosteric re-arrangement of GABA<sub>B</sub> receptor transmembrane domains towards an active conformation, culminating in receptor activation. Furthermore, we demonstrate that shear stress-induced GABA<sub>B</sub> receptor activation plays a crucial role in astrocyte remodeling. These findings reveal a role of GABA<sub>B</sub> receptor in mechano-transduction, uncovering a ligand-independent activation mechanism for GPCRs.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T14:49:00.051Z","creation":"2026-05-18T03:08:19.803Z"},"accession":"S-EPMC12595035","cross_references":{"pubmed":["41203595"],"doi":["10.1038/s41467-025-64811-2"]}}