Polyubiquitin-dependent recruitment of NEMO/IKKγ into T cell receptor signaling microclusters is controlled by IKKβ kinase activity

• DOI: 10.4049/jimmunol.204.supp.80.1
• Publication Date: 2023-01-01T15:34:42Z
• Authors: Nicholas Robert K...; Elizabeth DeRiso; Andrea L Szymczak...; Angela Montecalvo; Joanne M Murphy; Maria-Cristina Se...; Stephen C Bunnell; Lawrence P Kane
• Keywords: IκB kinase; Jurkat cells

Abstract The IkB kinase (IKK) complex coordinates inflammatory responses by activating canonical NFkB downstream of immune receptors. This consists the kinases IKKa/β and dimeric adaptor subunit NEMO (NFkB essential modulator protein). mutations cause immunodeficiencies impair antigen receptor function. Canonical activation immunoreceptors, such as T cell (TCR), requires assembly Carma1/Bcl10/Malt1 (CBM) signalosome. While, functional studies in vitro interactions, place IKK CBM signalosome, spatial relationship between these complexes has never been observed intact cells. We that is recruited into TCR microclusters membrane compartments within ~70 seconds engagement. Point impacting K63-linked linear polyubiquitin ubiquitin-binding domains selectively recruitment microclusters. verified involvement chains showing inhibitors either K63-specific Uev1A/Ubc13 ubiquitin E2 ligase or (LUBAC) prevent from entering To examine whether entire to TCR, we co-expressed IKKb chimeras with NEMO. wild-type (WT), but not kinase-dead, caused disappear. Similarly, treatment cells expressing WT IKKβ its upstream activator, TAK1, restored These results suggest via linear- then dissociates activity.