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By Dennis Keefe, Lianfa Shi, Stefan Feske, Ramiro Massol, Francisco Navarro, Tomas Kirchhausen and Judy Lieberman

Abstract

Perforin delivers granzymes to induce target-cell apoptosis. At high concentrations, perforin multimerizes in the plasma membrane to form pores. However, whether granzymes enter target cells via membrane pores is uncertain. Here we find that perforin at physiologically relevant concentrations and during cellmediated lysis creates pores in the target-cell membrane, transiently allowing Ca 2+ and small dyes into the cell. The Ca 2+ flux triggers a wounded membranerepair response in which internal vesicles, including lysosomes and endosomes, donate their membranes to reseal the damaged membrane. Perforin also triggers the rapid endocytosis of granzymes into large EEA-1-staining vesicles. The restoration of target-cell membrane integrity by triggering the repair response is necessary for target cells subjected to cytotoxic T lymphocyte attack to avoid necrosis and undergo the slower process of programmed cell death. Thus, the target cell actively participates in determining its own fate during cell-mediated death

Year: 2014
OAI identifier: oai:CiteSeerX.psu:10.1.1.418.450
Provided by: CiteSeerX
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