title: Construction of hybrid proteins that migrate retrogradely and transynaptically into the central nervous system.
abstract: The nontoxic proteolytic C fragment of tetanus toxin (TTC peptide) has the same ability to bind nerve cells and be retrogradely transported through a synapse as the native toxin. We have investigated its potential use as an in vivo neurotropic carrier. In this work we show that a hybrid protein encoded by the lacZ-TTC gene fusion retains the biological functions of both proteins in vivo-i.e. , retrograde transynaptic transport of the TTC fragment and beta-galactosidase enzymatic activity. After intramuscular injection, enzymatic activity could be detected in motoneurons and connected neurons of the brainstem areas. This strategy could be used to deliver a biological activity to neurons from the periphery to the central nervous system. Such a hybrid protein could also be used to map synaptic connections between neural cells.
authors.affiliation: Unité d'Embryologie Moléculaire, Unité de Recherche Associée 1947, Centre National de la Recherche Scientifique, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: L
authors.initials: L
authors.lastname: Coen
authors.forename: R
authors.initials: R
authors.lastname: Osta
authors.forename: M
authors.initials: M
authors.lastname: Maury
authors.forename: P
authors.initials: P
authors.lastname: Brûlet
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism*; D007763:Lac Operon; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013744:Tetanus Toxin / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin