C5a receptor explained

The C5a receptor also known as complement component 5a receptor 1 (C5AR1) or CD88 (Cluster of Differentiation 88) is a G protein-coupled receptor for C5a. It functions as a complement receptor.[1] C5a receptor 1 modulates inflammatory responses, obesity, development and cancers.[2] [3] [4] From a signaling transduction perspective, C5a receptor 1 activation is implicated in β-arrestin2 recruitment via Rab5a,[5] coupling of Gαi proteins,[6] ERK1/2 phosphorylation, [7] calcium mobilization and Rho activation[8] leading to downstream functions, such as secretion of cytokines, chemotaxis, and phagocytosis.

Cells

The C5a receptor 1 is expressed on:[9]

Agonist and antagonists

Potent and selective agonist and antagonists for C5a receptor 1 have been developed.[10] [11] [12] [13] [14] [15]

See also

Further reading

External links

Notes and References

  1. Gerard C, Gerard NP . C5A anaphylatoxin and its seven transmembrane-segment receptor . Annual Review of Immunology . 12 . 775–808 . 1994 . 8011297 . 10.1146/annurev.iy.12.040194.004015 .
  2. Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ . The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury . The Journal of Neuroscience . 35 . 16 . 6517–6531 . April 2015 . 25904802 . 6605214 . 10.1523/JNEUROSCI.5218-14.2015 .
  3. Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP . C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling . FASEB Journal . 27 . 2 . 822–831 . February 2013 . 23118029 . 10.1096/fj.12-220582 . free . 25562647 .
  4. Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, Coukos G, Lambris JD . Modulation of the antitumor immune response by complement . Nature Immunology . 9 . 11 . 1225–1235 . November 2008 . 18820683 . 2678913 . 10.1038/ni.1655 .
  5. Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J . Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages . Journal of Innate Immunity . 15 . 1 . 468–484 . March 2023 . 36882040 . 10.1159/000530012 . 10105068 .
  6. Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, Tian X, Wang B, Bin Y, Chen P, Yan W, Fu P, Shao Z . Mechanism of activation and biased signaling in complement receptor C5aR1 . Cell Research . 33 . 4 . 312–324 . April 2023 . 36806352 . 10.1038/s41422-023-00779-2 . 9937529 .
  7. Li XX, Lee JD, Massey NL, Guan C, Robertson AA, Clark RJ, Woodruff TM . Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function . Biochemical Pharmacology . 180 . 114156 . October 2020 . 32682759 . 10.1016/j.bcp.2020.114156 . 220653568 .
  8. Wang X, Iyer A, Lyons AB, Körner H, Wei W . Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages . Frontiers in Immunology . 10 . 2031 . 2019 . 31507616 . 6718513 . 10.3389/fimmu.2019.02031 . free .
  9. Klos A, Wende E, Wareham KJ, Monk PN . International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors . Pharmacological Reviews . 65 . 1 . 500–543 . January 2013 . 23383423 . 10.1124/pr.111.005223 . free .
  10. Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, Rolfe BE, Woodruff TM, Clark RJ . Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity . Journal of Medicinal Chemistry . 64 . 22 . 16598–16608 . November 2021 . 34762432 . 10.1021/acs.jmedchem.1c01174 . 244040645 .
  11. Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP . Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a . Journal of Medicinal Chemistry . 41 . 18 . 3417–3425 . August 1998 . 9719594 . 10.1021/jm9800651 .
  12. Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, Lommen GV, Hornby PJ, He W . Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists . Bioorganic & Medicinal Chemistry Letters . 18 . 14 . 3852–3855 . July 2008 . 18595693 . 10.1016/j.bmcl.2008.06.059 .
  13. Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, Kamahori T, Ehara S, Itoh K, Ohtsuka T, Ohbora T, Mishina T, Komatsu H, Naka Y . Identification of a potent and orally active non-peptide C5a receptor antagonist . The Journal of Biological Chemistry . 277 . 51 . 49403–49407 . December 2002 . 12384495 . 10.1074/jbc.M209672200 . free .
  14. Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, Kok WM, Stoermer MJ, Sweet MJ, Reid RC, Suen JY, Fairlie DP . Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists . Scientific Reports . 6 . 1 . 24575 . April 2016 . 27094554 . 4837355 . 10.1038/srep24575 . 2016NatSR...624575S .
  15. Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD . Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant . Journal of Immunology . 164 . 10 . 5492–5498 . May 2000 . 10799917 . 10.4049/jimmunol.164.10.5492 . 38942679 . free .