Antibodies to cell surface proteins redirect intracellular trafficking pathways

作者：St Pierre Christine A; Leonard Deborah; Corvera Silvia; Kurt Jones Evelyn A; Finberg Robert W^*

来源：Experimental and Molecular Pathology, 2011, 91(3): 723-732.

DOI：10.1016/j.yexmp.2011.05.011

• Endosomes
• Degradation
• Antibody
• Trafficking
• Internalization

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 C. 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.

• 出版日期2011-12