Tetanus neurotoxin (TeNT) is amongst the most poisonous substances on Earth and a major cause of neonatal death in non-vaccinated areas. Its very high toxicity is due to an exquisite tropism for the neuromuscular junction (NMJ) and its routing to the axonal transport pathway followed by transcytosis to spinal inhibitory interneurons, which causes a persistent spastic paralysis.
TeNT targets the NMJ with high affinity, yet the nature of the TeNT receptor complex was still lacking. We showed that nidogens are the main determinant for TeNT binding at the NMJ and it targets TeNT (as well as other physiological ligands) for sorting to axonal transport organelles. Understanding this mechanism is therefore crucial to better understand ligand sorting at the NMJ and uncovers novel means for tetanus control.