The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution

Latrophilin is a brain-specific Ca2+-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin, We now report the finding of two novel latrophilin homologues. All three latrophilins are unusual G protein-coupled receptors, They exhibit strong similarities,within their lectin, olfactomedin and transmembrane domains but possess variable C-termini, Latrophilins have up to seven sites of alternative splicing; some splice variants contain an altered third cytoplasmic loop or a truncated cytoplasmic tail, Only latriphilin-1 binds alpha-latrotoxin; it is abundant in brain and is present in endocrine cells. Latrophilin-3 is also brain-specific, whereas latrophilin-2 is ubiquitous, Together, latrophilins form a novel family of heterogeneous G protein-coupled receptors with distinct tissue distribution and functions. (C) 1999 Federation of European Biochemical Societies.