Signalosome

Signalosomes are large supramolecular protein complexes that combine by clustering (oligomerization or polymerization) and/or colloidal phase separation to form biomolecular condensates that increase the local concentration and signal transduction activity of the individual components. They are an example of molecular self-organization and self-assembly in cell biology.

Examples of signalosomes:

• Wnt signalosome: Transduction of Wnt signals from the plasma membrane depends on clustering of LRP6 receptors with Dishevelled (Dvl) proteins to recruit the axin complex for inactivation.
• B-cell receptor (BCR) signalosome: The B-cell receptor (BCR) binds antigens and clusters to induce signal transduction.
• T cell receptor (TCR) signalosome: Antigen presentation to T cells is recognized by the T cell receptor (TCR), which initiates clustering and activation of downstream signaling to trigger T cell responses.
• COP9 signalosome: Catalyzes the hydrolysis of the NEDD8 protein from the cullin subunit of the cullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for the deneddylation of CRL - at the same time it is able to bind the deneddylated cullin-RING complex and keep it in a deactivated form. The COP9 signalosome thus serves as the sole deactivator of CRLs.
• RIPK1/RIPK3 necrosome (see RIPK1 gene below): RIP (Receptor-Interacting Protein) family of serine/threonine protein kinases. The signaling complex is involved in necrotic cell death. RIPK1/RIPK3 kinase-mediated necrosis is called necroptosis.
• Inflammasomes: The inflammasomes AIM2 and NLRP3 are filamentous assemblies that trigger host defense in cells by activating caspase-1 for cytokine maturation and cell death.