Interleukin 1 signaling and receptor endocytosis

The pro-inflammatory cytokine IL-1 is a critical regulator of the innate immune response and the interleukin-1 (IL-1)-mediated signal transduction is a paradigm of immune signalling. IL-1 binding to IL-1 receptor I (IL-1RI) triggers initial signalling events that take place at the plasma membrane. However, IL-1RI is internalized rapidly upon ligand binding, but the function of the IL-1RI internalization remained elusive. Recently, we demonstrated a critical role for the internalization of IL-1RI in the IL-1-mediated signal transduction. We also showed that the small GTPase Rac1 is activated after receptor internalization which is key for the IL-1-induced gene expression. The small GTPase Rac1 is an endosome-specific “sorting adaptor” in IL-1 signaling. However, the mechanistic details of signalling remained elusive and will be addressed in future studies.