Antibodies to cell surface proteins redirect intracellular trafficking pathways.
Exp Mol Pathol
; 91(3): 723-32, 2011 Dec.
Article
in En
| MEDLINE
| ID: mdl-21819978
ABSTRACT
Antibody-mediated intracellular delivery of therapeutic agents has been considered for treatment of a variety of diseases. These approaches involve targeting cell-surface receptor proteins expressed by tumors or viral proteins expressed on infected cells. We examined the intracellular trafficking of a viral cell-surface-expressed protein, rabies G, with or without binding a specific antibody, ARG1. We found that antibody binding shifts the native intracellular trafficking pathway of rabies G in an Fc-independent manner. Kinetic studies indicate that the ARG1/rabies G complex progressively co-localized with clathrin, early endosomes, late endosomes, and lysosomes after addition to cells. This pathway was different from that taken by rabies G without addition of antibody, which localized with recycling endosomes. Findings were recapitulated using a cellular receptor with a well-defined endogenous recycling pathway. We conclude that antibody binding to cell-surface proteins induces redirection of intracellular trafficking of unbound or ligand bound receptors to a specific degradation pathway. These findings have broad implications for future developments of antibody-based therapeutics.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycoproteins
/
Viral Envelope Proteins
/
Protein Transport
/
Membrane Proteins
/
Antibodies
/
Antigens, Viral
Limits:
Animals
/
Humans
Language:
En
Journal:
Exp Mol Pathol
Year:
2011
Document type:
Article
Affiliation country:
United States