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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87687 |
| Date | 26 October 2023 |
| Creators | Mitgau, Jakob, Franke, Julius, Schinner, Camilla, Stephan, Gabriele, Berndt, Sandra, Placantonakis, Dimitris G., Kalwa, Hermann, Spindler, Volker, Wilde, Caroline, Liebscher, Ines |
| Publisher | Frontiers Media S.A. |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 873278 |
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