Interaction of tetanus toxin derived hybrid proteins with neuronal cells.
J Nat Toxins
; 9(4): 363-79, 2000 Nov.
Article
en En
| MEDLINE
| ID: mdl-11126515
The non-toxic ganglioside binding domain of tetanus toxin (Hc fragment C or TTC) has been studied as a vector for delivering therapeutic proteins to neurons. There is little information on the cellular processing of proteins delivered by linkage to TTC. We have evaluated the cellular handling of a multi-domain hybrid protein containing TTC and both the human enzyme superoxide dismutase and the maltose binding protein from E. coli. Binding, internalization, and cleavage of this protein during prolonged incubation with fetal cortical neurons or cells of the N18-RE-105 line was evaluated by immunoblot analysis, ELISA, and immunocytochemistry. Hybrid proteins were bound and internalized in a manner very similar to TTC. Internalized proteins showed long-term stability within cells, and were degraded into predictable large protein fragments in both cell types. Fragments that were cleaved away from the TTC domain were released into extracellular fluid after internalization. Proteins coupled to TTC share its long-term stability after cellular internalization. After internalization, dissociation of proteins linked to TTC facilitates their release from the cell, but not into other cellular compartments such as the cytosol. TTC linked proteins are probably enclosed within a stable endosomal compartment throughout their cellular lifetime.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa
/
Toxina Tetánica
/
Proteínas de Transporte de Monosacáridos
/
Proteínas
/
Proteínas Portadoras
/
Transportadoras de Casetes de Unión a ATP
/
Proteínas de Escherichia coli
/
Neuronas
Límite:
Humans
Idioma:
En
Revista:
J Nat Toxins
Asunto de la revista:
TOXICOLOGIA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos