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. [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]

Related Research Articles

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">Catenin beta-1</span> Mammalian protein found in humans

Catenin beta-1, also known as β-catenin (beta-catenin), is a protein that in humans is encoded by the CTNNB1 gene.

<span class="mw-page-title-main">AXIN1</span> Protein-coding gene in the species Homo sapiens

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.

<span class="mw-page-title-main">Proto-oncogene Wnt-1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene Wnt-1, or Proto-oncogene Int-1 homolog is a protein that in humans is encoded by the WNT1 gene.

<span class="mw-page-title-main">LRP5</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene. LRP5 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway. Mutations in LRP5 can lead to considerable changes in bone mass. A loss-of-function mutation causes osteoporosis pseudoglioma syndrome with a decrease in bone mass, while a gain-of-function mutation causes drastic increases in bone mass.

<span class="mw-page-title-main">DVL1</span> Human protein and coding gene

Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.

<span class="mw-page-title-main">LRP6</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

<span class="mw-page-title-main">COPS2</span> Protein-coding gene in humans

COP9 signalosome complex subunit 2 is a protein that in humans is encoded by the COPS2 gene. It encodes a subunit of the COP9 signalosome.

<span class="mw-page-title-main">CUL3</span> Protein-coding gene in humans

Cullin 3 is a protein that in humans is encoded by the CUL3 gene.

<span class="mw-page-title-main">COP9 signalosome complex subunit 3</span> Protein-coding gene in the species Homo sapiens

COP9 signalosome complex subunit 3 is a protein that in humans is encoded by the COPS3 gene. It encodes a subunit of the COP9 signalosome.

<span class="mw-page-title-main">COPS4</span> Protein-coding gene in humans

COP9 signalosome complex subunit 4 is a protein that in humans is encoded by the COPS4 gene.

<span class="mw-page-title-main">COPS8</span> Protein-coding gene in humans

COP9 signalosome complex subunit 8 is a protein that in humans is encoded by the COPS8 gene.

<span class="mw-page-title-main">GPS1</span> Protein-coding gene in the species Homo sapiens

COP9 signalosome complex subunit 1 is a protein that in humans is encoded by the GPS1 gene.

<span class="mw-page-title-main">DVL2</span> Human protein and coding gene

Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.

<span class="mw-page-title-main">COPS7A</span> Protein-coding gene in humans

COP9 signalosome complex subunit 7a is a protein that in humans is encoded by the COPS7A gene.

<span class="mw-page-title-main">RIPK3</span> Protein-coding gene in humans

Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that is encoded by the RIPK3 gene in humans.

<span class="mw-page-title-main">DKK2</span> Protein-coding gene in the species Homo sapiens

Dickkopf-related protein 2 is a protein in the Dickkopf family that in humans is encoded by the DKK2 gene.

<span class="mw-page-title-main">Dishevelled</span> Family of proteins

Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs. There are vertebrate homologs in zebrafish, Xenopus (Xdsh), mice and humans. Dsh relays complex Wnt signals in tissues and cells, in normal and abnormal contexts. It is thought to interact with the SPATS1 protein when regulating the Wnt Signalling pathway.

<span class="mw-page-title-main">COP9 signalosome</span>

COP9 signalosome (CSN) is a protein complex with isopeptidase activity. It 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 denedyllated cullin-RING complex and retain them in deactivated form. COP9 signalosome thus serves as a sole deactivator of CRLs. The complex was originally identified in plants, and subsequently found in all eukaryotic organisms including human. Human COP9 signalosome consists of 8 subunits - CSN1, CSN2, CSN3, CSN4, CSN5, CSN6, CSN7, CSN8. All are essential for full function of the complex and mutation in some of them is lethal in mice.

<span class="mw-page-title-main">Biomolecular condensate</span> Class of membrane-less organelles within biological cells

In biochemistry, biomolecular condensates are a class of membrane-less organelles and organelle subdomains, which carry out specialized functions within the cell. Unlike many organelles, biomolecular condensate composition is not controlled by a bounding membrane. Instead, condensates can form and maintain organization through a range of different processes, the most well-known of which is phase separation of proteins, RNA and other biopolymers into either colloidal emulsions, gels, liquid crystals, solid crystals or aggregates within cells.

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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