signalosomes

Signalosomes are multi-protein signaling complexes that assemble in response to receptor activation to coordinate transduction. They bring together receptors, adaptor or scaffold proteins, enzymes such as kinases and ubiquitin ligases, and substrates to create a functional unit that propagates cellular signals.

These assemblies are typically organized around scaffold or adaptor proteins that recruit and align signaling components. This arrangement concentrates signaling molecules in a small space, increasing reaction efficiency, specificity, and speed. Signalosomes are usually dynamic and reversible, forming at membranes or in the cytosol and disassembling when the signal subsides. Their composition can change over time, enabling sequential steps in a pathway and amplification of the signal.

Regulation occurs through post-translational modifications, changes in protein-protein interactions, lipid microdomains, and cytoskeletal context. Some signalosomes form via liquid-liquid phase separation, producing discrete, dynamic compartments that concentrate signaling reagents without a membrane boundary.

Well-characterized examples include inflammasomes, such as the NLRP3-ASC-caspase-1 complex, which activates inflammatory cytokines; the death-inducing signaling complex (DISC) composed of Fas receptor, FADD, and caspase-8 that initiates apoptosis; the Wnt signalosome, involving Dishevelled and other components that regulate beta-catenin signaling; and various Toll-like receptor and TNF receptor signaling platforms containing MyD88 or related adaptors.

Signalosomes play critical roles in innate immunity, development, and tissue homeostasis. Dysregulation of these assemblies can contribute to autoinflammatory diseases, cancer, and neurodegenerative disorders. The concept emphasizes coordinated, spatially organized signaling beyond linear cascades and encompasses evolving ideas about phase separation and dynamic multi-protein networks.