Latrophilin‐like receptor from the parasitic nematode Haemonchus contortus as target for the anthelmintic depsipeptide PF1022A

PF1022A belongs to a new class of cyclodepsipeptides with broad anthelmintic activity. Here, we describe a novel target for PF1022A. Using PF1022A ligand immunoscreening of a cDNA library constructed from the parasitic nematode Haemonchus contortus , we identified a 3539 bp cDNA encoding a novel orphan heptahelical transmembrane 110 kDa‐receptor, termed HC110‐ R, similar to the mammalian G‐protein coupled receptor latrophilin. HC110‐R is localized at plasma membranes and in intracellular vesicles of HC110‐R‐transfected HEK‐293 cells. The ligand of latrophilin, a‐latrotoxin (LTX), binds to the extracellular N ‐terminal region of HC110‐ R and induces influx of external Ca 2+ through Cd 2+ ‐ and nifedipine‐blockable Ca 2+ channels. PF1022A also binds to the N ‐terminus of HC110‐R and acts as an antagonist to LTX signaling in HC110‐R transfected HEK‐293 cells.