Biology:Signalosome
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]
References
- ↑ 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. doi:10.1016/S0960-9822(03)00370-1. ISSN 09609822.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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. doi:10.1126/science.1137065. ISSN 0036-8075.
- ↑ 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 09680004.
- ↑ Sear, Richard P. (2007). "Dishevelled: a protein that functions in living cells by phase separating". Soft Matter 3 (6): 680. doi:10.1039/b618126k. ISSN 1744-683X.
- ↑ Prabakaran, Sudhakaran (2015). "B cell receptor signaling dynamics". Science Signaling 8 (384): ec186–ec186. doi:10.1126/scisignal.aac9222. ISSN 1945-0877.
- ↑ Satpathy, Shankha; Wagner, Sebastian A; Beli, Petra; Gupta, Rajat; Kristiansen, Trine A; Malinova, Dessislava; Francavilla, Chiara; Tolar, Pavel et al. (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.
- ↑ 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 09527915.
- ↑ 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. doi:10.1038/nature13566. PMID 25043011. Bibcode: 2014Natur.512..161L.
- ↑ Li, Jixi; McQuade, Thomas; Siemer, Ansgar; Napetschnig, Johanna; Moriwaki, Kenta; Hsiao, Yu-Shan; Damko, Ermelinda; Moquin, David et al. (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 00928674.
- ↑ Lu, Alvin; Magupalli, Venkat Giri; Ruan, Jianbin; Yin, Qian; Atianand, Maninjay K.; Vos, Matthijn R.; Schröder, Gunnar F.; Fitzgerald, Katherine A. et al. (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 00928674.
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