Latrophilins (Latrophilin1-3) are members of the adhesion G-protein coupled receptor subfamily. Like all GPCRs, Latrophilins have seven transmembrane domains and are distinguished by a large extracellular N-terminal tail and a large intracellular C-terminal tail¹. The N-terminus has several cell adhesion domains and undergoes proteolysis after synthesis, while the C-terminal has various consensus post-translational sites like phosphorylation and palmitoylation². In addition, Latrophilins undergo alternative splicing³.

Latrophilin-1 was discovered by its ability to bind α-Latrotoxin (α-LTX), a toxin isolated from the black widow spider venom⁴. α-LTX induces exocytosis by creating a Ca²⁺ influx in the presynaptic membrane. α-LTX can also stimulate small vesicle exocytosis in a Ca²⁺ independent manner. Three receptors have been found to bind α-LTX. Of the three, Latrophilins are responsible for the Ca²⁺-independent effects of α-LTX². The binding of α-LTX to Latrophilin-1 increases exocytosis of neurotransmitters^5,6.

In an attempt to find the natural ligand of Latrophilin-1, Lasso, a splice variant of Teneneurin-2 was discovered to be an endogenous binding partner of the adhesion-GPCR⁷. Teneneurins are large glycoproteins with a single transmembrane domain^8,9. Like Latrophilin-1, Teneneurins are mostly expressed in the brain where they modulate neurite outgrowth, axon guidance and synaptogenesis⁷.

Regarding the localization of Latrophilins, Latrophilin-1 is expressed predominantly in the brain, Latrophilin-2 is highly expressed in the liver and lung, while Latrophilin-3 is almost exclusively detected in the brain^1,10.