title: Tetanus toxin entry. Nidogens are therapeutic targets for the prevention of tetanus.
abstract: Tetanus neurotoxin (TeNT) is among the most poisonous substances on Earth and a major cause of neonatal death in nonvaccinated areas. TeNT targets the neuromuscular junction (NMJ) with high affinity, yet the nature of the TeNT receptor complex remains unknown. Here, we show that the presence of nidogens (also known as entactins) at the NMJ is the main determinant for TeNT binding. Inhibition of the TeNT-nidogen interaction by using small nidogen-derived peptides or genetic ablation of nidogens prevented the binding of TeNT to neurons and protected mice from TeNT-induced spastic paralysis. Our findings demonstrate the direct involvement of an extracellular matrix protein as a receptor for TeNT at the NMJ, paving the way for the development of therapeutics for the prevention of tetanus by targeting this protein-protein interaction.
authors.affiliation: Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: Kinga
authors.initials: K
authors.lastname: Bercsenyi
authors.affiliation: Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmieg
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: J Barney
authors.initials: JB
authors.lastname: Bryson
authors.affiliation: Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Wallace
authors.affiliation: Department of Biomedical Sciences, University of Padua, Viale G. Colombo 3, 35131 Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caccin
authors.affiliation: Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Golding
authors.affiliation: Department of Biomedical Sciences, University of Padua, Viale G. Colombo 3, 35131 Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanotti
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Greensmith
authors.affiliation: Department of Dermatology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London WC1N 3BG, UK. giampietro.schiavo@ucl.ac.uk.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
mesh_terms: D000818:Animals; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013742:Tetanus / Q000517:prevention & control*; D013744:Tetanus Toxin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D008562:Membrane Glycoproteins; D010455:Peptides; D013744:Tetanus Toxin; C029967:nidogen; C035979:tetanospasmin; D008666:Metalloendopeptidases