ArticleNano letters2023
Unveiling Mechanical Activation: GAIN Domain Unfolding and Dissociation in Adhesion GPCRs.
Article in Nano letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Non-canonical cleavage of GPR125/ADGRA3 releases extracellular receptor fragments detectable in cerebrospinal fluid.iScience · 2026Article
- Tethered agonist- and GAIN domain-independent signaling of an adhesion GPCR.Science advances · 2026Article
- Protein force spectroscopy using magnetic tweezers: Slow and steady wins the race?Biophysical journal · 2026Review
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- CaRPOOL: a pooled calcium‑recording CRISPR screening platform identifies CCR7 as a modulator of cellular osmomechanosensing.Cell communication and signaling : CCS · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Genetic interaction betweenResearch square · 2026Article
- Genetic interaction betweenbioRxiv : the preprint server for biology · 2026Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Self-cleavage of the GAIN domain of adhesion G protein-coupled receptors requires multiple domain-extrinsic factors.Nature communications · 2025Article
- The Dissociation of Latrophilin Fragments by Perfluorooctanoic Acid (PFOA) Inhibits LTXToxins · 2025Article
- Decoding force-transmission linkages for therapeutic targeting and engineering.APL bioengineering · 2025Review
- Structural basis for regulation of CELSR1 by a compact module in its extracellular region.Nature communications · 2025Article
- Generic residue numbering of the GAIN domain of adhesion GPCRs.Nature communications · 2025Article
- Mechanical force induced activation of adhesion G protein-coupled receptor.Mechanobiology in medicine · 2024Review
- Multi-domain interaction mediated strength-building in human α-actinin dimers unveiled by direct single-molecule quantification.Nature communications · 2024Article
- Magnetogenetics as a promising tool for controlling cellular signaling pathways.Journal of nanobiotechnology · 2024Review
- Unraveling the Dual-Stretch-Mode Impact on Tension Gauge Tethers' Mechanical Stability.Journal of the American Chemical Society · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adhesion G protein-coupled receptors (aGPCRs) have extracellular regions (ECRs) containing GPCR autoproteolysis-inducing (GAIN) domains. The GAIN domain enables the ECR to self-cleave into N- and C-terminal fragments. However, the impact of force on the GAIN domain's conformation, critical for mechanosensitive aGPCR activation, remains unclear. Our study investigated the mechanical stability of GAIN domains in three aGPCRs (B, G, and L subfamilies) at a loading rate of 1 pN/s. We discovered that forces of a few piconewtons can destabilize the GAIN domains. In autocleaved aGPCRs ADGRG1/GPR56 and ADGRL1/LPHN1, these forces cause the GAIN domain detachment from the membrane-proximal Stachel sequence, preceded by partial unfolding. In noncleavable aGPCR ADGRB3/BAI3 and cleavage-deficient mutant ADGRG1/GPR56-T383G, complex mechanical unfolding of the GAIN domain occurs. Additionally, GAIN domain detachment happens during cell migration. Our findings support the mechanical activation hypothesis of aGPCRs, emphasizing the sensitivity of the GAIN domain structure and detachment to physiological force ranges.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.