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Vol. 17, Issue 5, 2166-2176, May 2006

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POLKADOTS Are Foci of Functional Interactions in T-Cell Receptor–mediated Signaling to NF-B

Jeremy S. Rossman ^*, Natalia G. Stoicheva ^*, Felicia D. Langel ^*, George H. Patterson , Jennifer Lippincott-Schwartz , and Brian C. Schaefer ^*

^* Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20814

Submitted October 26, 2005; Revised February 13, 2006; Accepted February 14, 2006
Monitoring Editor: Mark Ginsberg

Stimulation of the T-cell receptor (TCR) results in the activation of several transcription factors, including NF-B, that are crucial for T-cell proliferation and gain of effector functions. On TCR engagement, several proteins within the TCR-directed NF-B signaling pathway undergo dynamic spatial redistribution, but the significance of these redistribution events is largely unknown. We have previously described TCR-induced cytoplasmic structures called POLKADOTS (punctate and oligomeric killing or activating domains transducing signals) that are enriched in the NF-B signaling intermediate, Bcl10. We now show that these structures are formed only under conditions that promote efficient NF-B activation. Furthermore, POLKADOTS formation is dependent on functional domains of specific NF-B signal transducers. Through use of a photoactivatable GFP, we demonstrate that POLKADOTS contain both a highly stable and a rapidly equilibrating protein component. FRET analyses show that POLKADOTS are sites of enriched interactions between Bcl10 and partner signaling proteins. These observations strongly suggest that POLKADOTS are focal sites of dynamic information exchange between cytosolic intermediates in the process of TCR activation of NF-B.

Abbreviations used: APC, antigen-presenting cell; CARD, caspase recruitment domain; FRET, fluorescence resonance energy transfer; IS, immunological synapse; mKO, monomeric Kusabira-Orange; PA-GFP, photo-activatable GFP; POLKADOTS, punctate oligomeric killing and activating domains transducing signals; ROI, region of interest; TCR, T-cell receptor.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Brian C. Schaefer (bschaefer{at}usuhs.mil).

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