Introduction of C5AR2
C5AR2 is one of the receptors of C5a, which is a potent peptide chemoattractant and an effective inflammatory mediator. It was discovered in 2000 and, despite its relatively short history, its function has been the subject of controversy. The receptor falls within the larger 7-transmembrane G-protein coupled receptor family and binding with C5a occurs with contribution from all extracellular domains of the receptor. On the intracellular domains, C5AR2 lacks the conserved residues necessary for G-protein coupling. As a result, C5AR2 is generally described as a modulator of C5AR1 signaling, exerting either anti- or pro-inflammatory activities. On one hand, C5AR2 may mediate anti-inflammatory effects by controlling the availability of C5a for the other receptor, C5AR1. On the other hand, it may induce G protein-independent activation of immune cells, thus exerting pro-inflammatory effects.
|Basic Information of C5AR2|
|Protein Name||C5a anaphylatoxin chemotactic receptor 2|
|Aliases||Complement component 5a receptor 2, G-protein coupled receptor 77|
|Organism||Homo sapiens (Human)|
Functions of C5AR2 Membrane Protein
The functions of C5AR2 have not been well-characterized. The involvement of C5AR2 in different diseases, such as neurodegenerative diseases, obesity, atherosclerosis, have been reported. Firstly, studies have suggested a pathogenic role for C5aR2 in mouse models of Huntington’s disease and Parkinson’s disease, and they are potential complement therapeutic targets to mitigate neuropathology in these diseases. Secondly, studies of the C5AR2-deficient mice support an anti-inflammatory/neuroprotective role for this receptor in the context of spinal cord injury. Moreover, C5AR2 deficiency is found to attenuate atherosclerosis and neointimal plaque formation after arterial injury. This identifies C5aR2 as a promising target to reduce atherosclerosis and restenosis after vascular interventions. Thirdly, animal and clinical data have supported the involvement of this receptor in obesity and in metabolism. However, the functions of C5AR2 remains controversial and needs to be found out in the future.
Fig.1 Targeting C5aR2 in immune cell regulation. (Kemper, 2016)
Applications of C5AR2 Membrane Protein in Literature
1. Pundir P., et al. The novel receptor C5aR2 is required for C5a-mediated human mast cell adhesion, migration, and proinflammatory mediator production. Journal of Immunology. 2015, 195(6): 2774-2787. PMID: 26283482
In this study, the investigators used human mast cell line Laboratory of Allergic Diseases 2 (LAD2 cells) as a model to study C5a/C5aR2-induced biological responses and signaling in human mast cells. The results demonstrated that C5aR2 ligation initiated a β-arrestin-2-, PI3K-, and ERK-dependent signaling pathway in these cells.
2. Croker D E., et al. Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signaling. Immunology & Cell Biology. 2016, 94(8): 787-95. PMID: 27108698
In this study, a library of 61 peptides based on the C-terminus of C5a was assayed for the ability to selectively modulate C5aR2 function. Functionally selective ligands for C5aR2 were selected and regarded as valuable tools to interrogate C5aR2 function.
3. Poppelaars F., et al. Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury. The FASEB Journal. 2017, 31(7): 3193-3204. PMID: 28396344
This study investigated the role of C5aR2 in the pathogenesis of renal ischemia-reperfusion (IR) injury by using wild-type and C5aR2-deficient mice. The results showed that C5aR2-deficient mice were protected from renal IR injury and it might play a more important role than C5aR1. It may provide a new target for IR intervention.
4. Biggins P., et al. The alternative receptor for complement component 5a, C5aR2, conveys neuroprotection in traumatic spinal cord injury. Journal of Neurotrauma. 2017, 34(12): 2075-2085. PMID: 28173736
This study demonstrated that C5aR2 receptor played a neuroprotective role in traumatic spinal cord injury and might be a novel target to restrain injurious C5a signaling after a major neurotraumatic event.
5. Karsten C M., et al. Tissue Destruction in Bullous Pemphigoid Can Be Complement Independent and May Be Mitigated by C5aR2. Frontiers in Immunology. 2018, 9: 488. PMID: 29599777
This study investigated the role of complement components, C5aR2 and C5aR1, in bullous pemphigoid. The results showed that these two receptors might play an opposing role in the mediation of the mentioned disease.
C5AR2 Preparation Options
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