Coalescence of Nanoscale Cytoplasmic Signalosomes Contributes to T Cell Receptor Signaling to NF-κB

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.52-52.13
• Main Authors: Traver, Maria K, Campanello, Leonard, Paul, Suman, Shroff, Hari, Losert, Wolfgang, Schaefer, Brian C
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.52.13

T cell receptor (TCR) activation of the transcription factor NF-κB is a crucial determinant of effector T lymphocyte function. The complex regulatory network surrounding this pathway remains poorly understood, particularly at time periods further removed from initial TCR triggering. We have previously demonstrated that following activation of the TCR, the proteins p62, Bcl10, and Malt1 rapidly combine to form a cytoplasmic filamentous signalosome called POLKADOTS, which recruits further signaling proteins and initiates the terminal steps in activation of NF-κB. Here, we examine the fate of POLKADOTS signalosomes following initial activation of NF-κB. We demonstrate via super-resolution and confocal microscopy techniques that POLKADOTS filaments converge on the microtubule-organizing center via microtubule transport, aggregating in a peri-nuclear aggresomal structure. Aggresomes are poorly understood structures thought to be depots of misfolded protein destined for degradation; however, our data suggest that the aggresomal accumulations of POLKADOTS continue to promote T cell activation. We show that the formation and maintenance of this aggresome corresponds with a secondary increase in NF-κB translocation. Additionally, the aggresomal structure prolongs phosphorylation of IKK and promotes the proteolytic activity of Malt1. Together, these results demonstrate that TCR signaling to NF-κB directs the orchestrated assembly, transport, and stable coalescence of nanoscale cytoplasmic signaling complexes. More broadly, our findings provide evidence that aggresomes can serve as stable platforms of signal transduction, thereby proposing a new role for these little understood structures.