Research ArticleImmunology

A Targeted siRNA Screen Identifies Regulators of Cdc42 Activity at the Natural Killer Cell Immunological Synapse

Sci. Signal.  29 Nov 2011:
Vol. 4, Issue 201, pp. ra81
DOI: 10.1126/scisignal.2001729

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Oscillatory Behavior at the Immunological Synapse

Natural killer (NK) cells are required for effective immune responses against virally infected cells and tumor cells. The activity of NK cells is controlled by coordinated signals from stimulatory and inhibitory receptors at the cell surface, which are engaged when the NK cell forms conjugates with target cells. Effective cell killing by NK cells is dependent on changes in the actin cytoskeleton that require Rho family GTPases, such as Cdc42. Carlin et al. used fluorescence-based live-cell imaging to show that after an initial “spike,” the activity of Cdc42 at the NK cell–target cell interface oscillated over time. Bioinformatics analysis and a short inhibitory RNA (siRNA)–based screen identified Akt and a subunit of PI3K as required for the stimulation and oscillation of Cdc42 activity, as well as for the polarization of cytotoxic vesicles, a critical step in NK cell cytotoxicity.