Document Detail


Interaction of tetanus toxin derived hybrid proteins with neuronal cells.
MedLine Citation:
PMID:  11126515     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D M Figueiredo; C C Matthews; D A Parks; N F Fairweather; G Dougan; S G Wilt; P S Fishman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of natural toxins     Volume:  9     ISSN:  1058-8108     ISO Abbreviation:  J Nat Toxins     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-13     Completed Date:  2001-02-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9208016     Medline TA:  J Nat Toxins     Country:  United States    
Other Details:
Languages:  eng     Pagination:  363-79     Citation Subset:  IM    
Affiliation:
Neurology Service and, Department of Neurology, Baltimore VAMC, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters*
Binding Sites
Carrier Proteins / metabolism*
Drug Delivery Systems
Enzyme-Linked Immunosorbent Assay
Escherichia coli / chemistry
Escherichia coli Proteins*
Humans
Immunoblotting
Immunoconjugates
Immunohistochemistry
Monosaccharide Transport Proteins*
Neurons / drug effects*,  enzymology
Proteins / administration & dosage,  chemistry,  pharmacokinetics*
Superoxide Dismutase / metabolism*
Tetanus Toxin / chemistry,  pharmacokinetics,  pharmacology*
Grant Support
ID/Acronym/Agency:
1-PO1-AG12992-01/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Carrier Proteins; 0/Escherichia coli Proteins; 0/Immunoconjugates; 0/Monosaccharide Transport Proteins; 0/Proteins; 0/Tetanus Toxin; 0/maltose transport system, E coli; 0/maltose-binding protein; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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