POLKADOTS are foci of functional interactions in T-Cell receptor-mediated signaling to NF-kappaB.
Stimulation of the T-cell receptor (TCR) results in the activation of several transcription factors, including NF-kappaB, that are crucial for T-cell proliferation and gain of effector functions. On TCR engagement, several proteins within the TCR-directed NF-kappaB 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-kappaB signaling intermediate, Bcl10. We now show that these structures are formed only under conditions that promote efficient NF-kappaB activation. Furthermore, POLKADOTS formation is dependent on functional domains of specific NF-kappaB 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-kappaB.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Jeremy S
JS
Rossman
Natalia G
NG
Stoicheva
Felicia D
FD
Langel
George H
GH
Patterson
Jennifer
J
Lippincott-Schwartz
Brian C
BC
Schaefer
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000074018:B-Cell CLL-Lymphoma 10 Protein; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000819:agonists / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000648:ultrastructure*
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D020169:Caspases; C498509:Malt1 protein, mouse; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein