2003. Regulation of lymphocyte-mediated killing by GTP-binding proteins

Abstract: Exocytosis of granules containing ap-optosis-inducing proteins is one mechanism of tar-get cell killing by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Granules containing perforin and granzymes are redistributed to the area of cell contact initiated by specific interac-tions between surface ligands on a target cell and receptors on an effector lymphocyte. The forma-tion of a stable conjugate between a cytotoxic lym-phocyte and its potential target cell, followed by the directed delivery of granule components to the target cell are prerequisites of lymphocyte-medi-ated killing. Critical to understanding the develop-ment of cytotoxic function by CTLs and NK cells is the delineation of the second messenger pathways that specifically control the reorganization of the actin cytoskeleton during cell-mediated cytotoxic-ity. The low molecular weight guanosine 5-triphosphate-binding proteins of the Rho family play a central role in these regulatory events con-trolling cytotoxic lymphocyte activation. J. Leu-koc. Biol. 73: 333–338; 2003. Key Words: natural killer cells cytotoxic T lymphocytes Rho GTPase family second messengers signal transductio