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Signalosome

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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.

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

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.

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.

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

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.

References

  1. Cliffe, Adam; Hamada, Fumihiko; Bienz, Mariann (2003). "A Role of Dishevelled in Relocating Axin to the Plasma Membrane during Wingless Signaling". Current Biology. 13 (11): 960–966. Bibcode:2003CBio...13..960C. doi:10.1016/S0960-9822(03)00370-1. ISSN 0960-9822. PMID 12781135.
  2. Schwarz-Romond, T. (2005). "The Wnt signalling effector Dishevelled forms dynamic protein assemblies rather than stable associations with cytoplasmic vesicles". Journal of Cell Science. 118 (22): 5269–5277. doi:10.1242/jcs.02646. ISSN 0021-9533. PMID 16263762.
  3. Schwarz-Romond, Thomas; Fiedler, Marc; Shibata, Naoki; Butler, P Jonathan G; Kikuchi, Akira; Higuchi, Yoshiki; Bienz, Mariann (2007). "The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization". Nature Structural & Molecular Biology. 14 (6): 484–492. doi:10.1038/nsmb1247. ISSN 1545-9993. PMID 17529994.
  4. Schwarz-Romond, T.; Metcalfe, C.; Bienz, M. (2007). "Dynamic recruitment of axin by Dishevelled protein assemblies". Journal of Cell Science. 120 (14): 2402–2412. doi:10.1242/jcs.002956. ISSN 0021-9533. PMID 17606995.
  5. Bilic, J.; Huang, Y.-L.; Davidson, G.; Zimmermann, T.; Cruciat, C.-M.; Bienz, M.; Niehrs, C. (2007). "Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation". Science. 316 (5831): 1619–1622. Bibcode:2007Sci...316.1619B. doi:10.1126/science.1137065. ISSN 0036-8075. PMID 17569865.
  6. Bienz, Mariann (2014). "Signalosome assembly by domains undergoing dynamic head-to-tail polymerization". Trends in Biochemical Sciences. 39 (10): 487–495. doi:10.1016/j.tibs.2014.08.006. ISSN 0968-0004. PMID 25239056.
  7. Sear, Richard P. (2007). "Dishevelled: a protein that functions in living cells by phase separating". Soft Matter. 3 (6): 680–684. Bibcode:2007SMat....3..680S. doi:10.1039/b618126k. ISSN 1744-683X. PMID 32900127.
  8. Prabakaran, Sudhakaran (2015). "B cell receptor signaling dynamics". Science Signaling. 8 (384): ec186. doi:10.1126/scisignal.aac9222. ISSN 1945-0877.
  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 (2015). "Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation". Molecular Systems Biology. 11 (6): 810. doi:10.15252/msb.20145880. ISSN 1744-4292. PMC 4501846. PMID 26038114.
  10. Werlen, Guy; Palmer, Ed (2002). "The T-cell receptor signalosome: a dynamic structure with expanding complexity". Current Opinion in Immunology. 14 (3): 299–305. doi:10.1016/S0952-7915(02)00339-4. ISSN 0952-7915. PMID 11973126.
  11. Lingaraju, GM; Bunker, RD; Cavadini, S; Hess, D; Hassiepen, U; Renatus, M; Fischer, ES; Thomä, NH (14 August 2014). "Crystal structure of the human COP9 signalosome". Nature. 512 (7513): 161–5. Bibcode:2014Natur.512..161L. doi:10.1038/nature13566. PMID 25043011.
  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 (2012). "The RIP1/RIP3 Necrosome Forms a Functional Amyloid Signaling Complex Required for Programmed Necrosis". Cell. 150 (2): 339–350. doi:10.1016/j.cell.2012.06.019. ISSN 0092-8674. PMC 3664196. PMID 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. (2014). "Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes". Cell. 156 (6): 1193–1206. doi:10.1016/j.cell.2014.02.008. ISSN 0092-8674. PMC 4000066. PMID 24630722.


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