Signalosome Explained

Signalosomes are large supramolecular protein complexes that undergo clustering (oligomerisation or polymerisation) and/or colloidal phase separation to form biomolecular condensates that increase the local concentration and signalling activity of the individual components. They are an example of molecular self-assembly and self-organisation in cell biology.

Examples

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.[1] [2] [3] [4] [5] [6] [7]

B-cell receptor (BCR) signalosome: The B-cell receptor (BCR) binds antigen and undergoes clustering to induce signal transduction.[8] [9]

T-cell receptor (TCR) signalosome: Antigen presentation to T-cells is recognised by the T-cell receptor (TCR), which initiates clustering and activation of downstream signalling to induce T-cell responses.[10]

COP9 signalosome

Catalyses the hydrolysis of NEDD8 protein from the Cullin subunit of Cullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for CRL deneddylation – at the same time, it is able to bind deneddylated cullin-RING complex and retain them in deactivated form. COP9 signalosome thus serves as a sole deactivator of CRLs.[11]

RIP1/RIP3 Necrosome: A signalling complex involved in necrotic cell death.[12]

Inflammasomes: The AIM2 and NLRP3 inflammasomes are filamentous assemblies that elicit host defense inside cells by activating caspase-1 for cytokine maturation and cell death.[13]

Notes and References

  1. Cliffe. Adam. Hamada. Fumihiko. Bienz. Mariann. A Role of Dishevelled in Relocating Axin to the Plasma Membrane during Wingless Signaling. Current Biology. 13. 11. 2003. 960–966. 0960-9822. 10.1016/S0960-9822(03)00370-1. free. 12781135 . 2003CBio...13..960C .
  2. Schwarz-Romond. T.. The Wnt signalling effector Dishevelled forms dynamic protein assemblies rather than stable associations with cytoplasmic vesicles. Journal of Cell Science. 118. 22. 2005. 5269–5277. 0021-9533. 10.1242/jcs.02646. 16263762 .
  3. Schwarz-Romond. Thomas. Fiedler. Marc. Shibata. Naoki. Butler. P Jonathan G. Kikuchi. Akira. Higuchi. Yoshiki. Bienz. Mariann. The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization. Nature Structural & Molecular Biology. 14. 6. 2007. 484–492. 1545-9993. 10.1038/nsmb1247. 17529994 .
  4. Schwarz-Romond. T.. Metcalfe. C.. Bienz. M.. Dynamic recruitment of axin by Dishevelled protein assemblies. Journal of Cell Science. 120. 14. 2007. 2402–2412. 0021-9533. 10.1242/jcs.002956. 17606995 .
  5. Bilic. J.. Huang. Y.-L.. Davidson. G.. Zimmermann. T.. Cruciat. C.-M.. Bienz. M.. Niehrs. C.. Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation. Science. 316. 5831. 2007. 1619–1622. 0036-8075. 10.1126/science.1137065. 17569865 . 2007Sci...316.1619B .
  6. Bienz. Mariann. Signalosome assembly by domains undergoing dynamic head-to-tail polymerization. Trends in Biochemical Sciences. 39. 10. 2014. 487–495. 0968-0004. 10.1016/j.tibs.2014.08.006. 25239056 .
  7. Sear. Richard P.. Dishevelled: a protein that functions in living cells by phase separating. Soft Matter. 3. 6. 2007. 680–684. 1744-683X. 10.1039/b618126k. 32900127 . 2007SMat....3..680S .
  8. Prabakaran. Sudhakaran. B cell receptor signaling dynamics. Science Signaling. 8. 384. 2015. ec186. 1945-0877. 10.1126/scisignal.aac9222.
  9. Satpathy. Shankha. Wagner. Sebastian A. Beli. Petra. Gupta. Rajat. Kristiansen. Trine A. Malinova. Dessislava. Francavilla. Chiara. Tolar. Pavel. Bishop. Gail A. Hostager. Bruce S. Choudhary. Chunaram. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation. Molecular Systems Biology. 11. 6. 2015. 810. 1744-4292. 10.15252/msb.20145880. 4501846. free. 26038114 .
  10. Werlen. Guy. Palmer. Ed. The T-cell receptor signalosome: a dynamic structure with expanding complexity. Current Opinion in Immunology. 14. 3. 2002. 299–305. 0952-7915. 10.1016/S0952-7915(02)00339-4. 11973126 .
  11. Lingaraju. GM. Bunker. RD. Cavadini. S. Hess. D. Hassiepen. U. Renatus. M. Fischer. ES. Thomä. NH. Nicolas H. Thomä. Crystal structure of the human COP9 signalosome.. Nature. 14 August 2014. 512. 7513. 161–5. 25043011. 10.1038/nature13566. 2014Natur.512..161L.
  12. Li. Jixi. McQuade. Thomas. Siemer. Ansgar. Napetschnig. Johanna. Moriwaki. Kenta. Hsiao. Yu-Shan. Damko. Ermelinda. Moquin. David. Walz. Thomas. McDermott. Ann. Chan. Francis. Wu. Hao. The RIP1/RIP3 Necrosome Forms a Functional Amyloid Signaling Complex Required for Programmed Necrosis. Cell. 150. 2. 2012. 339–350. 0092-8674. 10.1016/j.cell.2012.06.019 . 3664196. free. 22817896 .
  13. Lu. Alvin. Magupalli. Venkat Giri. Ruan. Jianbin. Yin. Qian. Atianand. Maninjay K.. Vos. Matthijn R.. Schröder. Gunnar F.. Fitzgerald. Katherine A.. Wu. Hao. Egelman. Edward H.. Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes. Cell. 156. 6. 2014. 1193–1206. 0092-8674. 10.1016/j.cell.2014.02.008. 4000066. free. 24630722 .

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