Latrophilin (LPHN)

Latrophilins are a family of three Adhesion G protein-coupled receptors (ADGRL1, ADGRL2, and ADGRL3) that are predominantly expressed in the brain and play vital roles in synapse development and function [UniProt]. They were first discovered as the primary targets for alpha-latrotoxin, a component of black widow spider venom that induces massive, calcium-independent release of neurotransmitters [Südhof, 2001]. These receptors function as cell-adhesion molecules, interacting with presynaptic and postsynaptic partners such as Teneurins and FLRT proteins to facilitate the assembly and maintenance of synaptic connections [Silva et al., 2011]. Latrophilin-3 (ADGRL3), in particular, has been identified as a significant susceptibility gene for Attention-Deficit/Hyperactivity Disorder (ADHD) and is associated with other neurodevelopmental disorders like autism and schizophrenia [Arcos-Burgos et al., 2010]. In veterinary medicine, latrophilin-like receptors in nematodes are the target of the anthelmintic drug emodepside, which causes parasite paralysis by modulating synaptic transmission [Harder et al., 2003]. Research into latrophilins continues to expand, focusing on their potential as therapeutic targets for cognitive and behavioral disorders due to their central role in neural circuitry and synaptic adhesion [Araç et al., 2012].

Other names

Adhesion G protein-coupled receptor LADGRLCalcium-independent receptor for alpha-latrotoxinCIRLLectomedin

Agonism of the receptor, leading to G-protein activation (typically Gq/11 or Gs) and subsequent massive, calcium-independent neurotransmitter exocytosis or modulation of synaptic adhesion and transmission [Südhof, 2001; Harder et al., 2003].