Adhesion G protein-coupled receptor L3 (ADGRL3)

ADGRL3 (Adhesion G protein-coupled receptor L3, also known as Latrophilin-3) is a member of the latrophilin subfamily of adhesion GPCRs, distinguished by an extracellular N-terminal region containing lectin, olfactomedin, and hormone-binding domains, followed by a conserved autoproteolysis-inducing (GAIN/GPS) domain and a seven-transmembrane domain[2][4]. It participates in both cell adhesion and metabotropic signaling, mediating synapse specificity, neuronal interactions, and plasticity, especially in the central nervous system. Human genetic studies implicate ADGRL3 in risk for ADHD and substance use disorders, and animal models reveal its influence on dopamine signaling and hyperactivity. Upon activation, ADGRL3 couples most robustly to the G12/13 class of heterotrimeric G proteins (regulating Rho GTPases and cytoskeletal responses), and also interacts with β-arrestin proteins, modulating ERK signaling. Functional disruption of ADGRL3 alters dopamine levels and exacerbates neurobehavioral phenotypes; it is considered a novel but orphan drug target, as endogenous ligands and selective drugs remain unidentified[1][2][3][4][5].

Other names

KIAA0768LEC3CIRL-3CIRL3CL3LPHN3Lectomedin-3Calcium-independent alpha-latrotoxin receptor 3Latrophilin-3latrophilin homolog 3 (cow)lectomedin 3

Modulation of downstream signaling via coupling with various G protein subtypes (particularly G12/13 and Gq); Signal transmission through β-arrestin recruitment, which can inhibit ERK phosphorylation[3]