TRAM Protein Identified as Key Regulator of Myddosome Maturation in Innate Immunity
A new study in Nature reveals that the protein TRAM is essential for the maturation of myddosomes, which are cytosolic signaling complexes derived from Toll-like receptors (TLRs). TRAM facilitates the release of MyD88 from membrane-bound proto-myddosomes, allowing them to mature into stable, enzyme-rich structures that sustain long-term inflammatory signaling. Without TRAM, MyD88 remains trapped at the plasma membrane, leading to premature termination of immune signals and reduced expression of secondary response genes. This mechanism explains how TLRs achieve hours-long NF-κB activation and durable cytokine production, providing a molecular basis for receptor-free signal transduction in innate immunity.