{"doi":"10.3389/fcell.2022.873278","title":"The N Terminus of Adhesion G Protein–Coupled Receptor GPR126/ADGRG6 as Allosteric Force Integrator","abstract":"The adhesion G protein-coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the receptor an attractive pharmacological target. GPR126 is a mechano-sensor that translates the binding of extracellular matrix (ECM) molecules to its N terminus into a metabotropic intracellular signal. To date, the structural requirements and the character of the forces needed for this ECM-mediated receptor activation are largely unknown. In this study, we provide this information by combining classic second-messenger detection with single-cell atomic force microscopy. We established a monoclonal antibody targeting the N terminus to stimulate GPR126 and compared it to the activation through its known ECM ligands, collagen IV and laminin 211. As each ligand uses a distinct mode of action, the N terminus can be regarded as an allosteric module that can fine-tune receptor activation in a context-specific manner.","journal":"Frontiers in Cell and Developmental Biology","year":2022,"id":247792,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":813766,"name":"Julius Franke","orcid":null,"position":1,"is_corresponding":false},{"id":813132,"name":"Camilla Schinner","orcid":"0000-0002-0450-7488","position":2,"is_corresponding":false},{"id":403622,"name":"Gabriele Stephan","orcid":null,"position":3,"is_corresponding":false},{"id":498923,"name":"Sandra Berndt","orcid":"0000-0002-9732-9413","position":4,"is_corresponding":false},{"id":402724,"name":"Dimitris G. Placantonakis","orcid":"0000-0003-1950-2978","position":5,"is_corresponding":false},{"id":813133,"name":"Hermann Kalwa","orcid":"0000-0002-4930-457X","position":6,"is_corresponding":false},{"id":605572,"name":"Volker Spindler","orcid":"0000-0002-1302-5421","position":7,"is_corresponding":false},{"id":586876,"name":"Caroline Wilde","orcid":"0000-0003-4548-1760","position":8,"is_corresponding":false},{"id":402721,"name":"Ines Liebscher","orcid":"0000-0003-4480-8987","position":9,"is_corresponding":false},{"id":813765,"name":"Jakob Mitgau","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:23:57.824223Z","pmid":"35813217","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}