ALPHA-LATROTOXIN RECEPTOR, LATROPHILIN, IS A NOVEL MEMBER OF THE SECRETIN FAMILY OF G-PROTEIN-COUPLED RECEPTORS

alpha-Latrotoxin (LTX) stimulates massive exocytosis of synaptic vesic les and mag help to elucidate the mechanism of regulation of neurosecr etion, We have recently isolated latrophilin, the synaptic Ca2+-indepe ndent LTX receptor. Now we demonstrate that latrophilin is a novel mem ber of the secretin family of G protein-coupled receptors that are inv olved in secretion, Northern blot analysis shows that latrophilin mess age is present only in neuronal tissue, Upon expression in COS cells, the cloned protein is indistinguishable from brain latrophilin and bin ds LTX with high affinity, Latrophilin physically interacts with a G a lpha(o) subunit of heterotrimeric G proteins, because the two proteins co-purify in a two-step affinity chromatography, interestingly, extra cellular domain of latrophilin is homologous to olfactomedin, a solubl e neuronal protein thought to participate in odorant binding, Our find ings suggest that latrophilin may bind unidentified endogenous ligands and transduce signals into nerve terminals, thus implicating G protei ns in the control of synaptic vesicle exocytosis.