TRAM promotes Toll-like-receptor-free myddosome signal transduction.
- Open access
TRAM enables receptor-free myddosome formation, sustaining hours-long NF-κB activation and inflammatory gene expression in TLR signaling.
- Why it matters: Understanding how proto-myddosomes mature into stable, receptor-free myddosomes is crucial for revealing mechanisms of prolonged inflammatory responses, which are key in immune regulation and disease.
- What they did: A genetic screen in macrophages identified TRAM as a regulator of myddosome assembly; biochemical and live-cell imaging showed TRAM facilitates MyD88 dissociation from TLR complexes, promoting maturation.
- The result: Disrupting cytosolic myddosomes with chemicals reduced inflammatory activity, highlighting TRAM’s role in receptor-independent signal transduction and offering potential targets for controlling inflammation.