Antibodies to cell surface proteins redirect intracellular trafficking pathways

Exp Mol Pathol. 2011 Dec;91(3):723-32. doi: 10.1016/j.yexmp.2011.05.011. Epub 2011 Jul 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Antigen-Antibody Reactions
  • Antigens, Viral* / immunology
  • Antigens, Viral* / metabolism
  • Cell Line, Tumor
  • Glycoproteins* / immunology
  • Glycoproteins* / metabolism
  • HEK293 Cells
  • Humans
  • Membrane Proteins* / immunology
  • Membrane Proteins* / metabolism
  • Mice
  • Plasmids
  • Protein Binding
  • Protein Transport / immunology*
  • Receptors, Transferrin / immunology
  • Receptors, Transferrin / metabolism
  • Signal Transduction
  • Transfection
  • Transferrin
  • Viral Envelope Proteins* / immunology
  • Viral Envelope Proteins* / metabolism


  • Antibodies
  • Antigens, Viral
  • Glycoproteins
  • Membrane Proteins
  • Receptors, Transferrin
  • Transferrin
  • Viral Envelope Proteins
  • glycoprotein G, Rabies virus