5 research outputs found
The N Terminus of Adhesion G Protein–Coupled Receptor GPR126/ ADGRG6 as Allosteric Force Integrator
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