Adhesion G-protein coupled receptor (aGPCR)

Adhesion G-protein coupled receptors (aGPCRs) are a distinct family of 33 receptors in humans, characterized by exceptionally large, modular N-terminal extracellular domains and a conserved GPCR autoproteolysis-inducing (GAIN) domain [1, 3, 11]. These receptors serve as essential molecular bridges, integrating chemical, adhesive, and mechanical signals to regulate cell-cell and cell-matrix interactions [5, 9, 11]. They play pivotal roles in diverse physiological processes, including neural development, immune system regulation, and organogenesis [2, 9, 11]. A hallmark of aGPCR function is their unique activation mechanism, which often involves the unmasking of an internal tethered agonist sequence, known as the Stachel, following mechanical force or proteolytic cleavage [1, 9, 12]. Although no drugs are currently approved to target this family, aGPCRs are highly significant therapeutic targets due to their strong associations with cancer metastasis, neurodevelopmental disorders, and inflammatory diseases [1, 2, 9]. Current research is actively exploring the use of monoclonal antibodies and synthetic peptides to modulate these complex signaling platforms for therapeutic benefit [2, 9, 12].

Other names

Adhesion GPCRsGRAFS family (Adhesion class)LNB-TM7 receptorsClass B2 GPCRsLong N-terminal domain 7-TM receptors

Tethered peptide activation (Stachel-mediated), Agonism, Allosteric modulation, Mechanosensory activation