complement component C5a receptor activity

Definition

Target type: molecularfunction

Combining with the C5a product of the complement cascade and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:add, GOC:mah, GOC:pg, GOC:signaling, ISBN:0781735149]

Complement component C5a receptor (C5aR) activity is a molecular function that involves the binding and signaling of the anaphylatoxin C5a, a potent pro-inflammatory peptide released during the complement cascade activation. C5aR is a G protein-coupled receptor (GPCR) expressed primarily on immune cells like neutrophils, macrophages, and mast cells. Upon C5a binding, C5aR triggers a signaling cascade through its association with heterotrimeric G proteins, primarily Gαi and Gαq. This activation leads to downstream signaling pathways, including:

1. **Phospholipase C (PLC) activation:** Gαq stimulation activates PLC, which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium, while DAG activates protein kinase C (PKC).

2. **Mitogen-activated protein kinase (MAPK) activation:** C5aR signaling activates various MAPK pathways, including ERK, JNK, and p38, leading to the regulation of gene expression and cellular responses.

3. **Activation of Rho GTPases:** C5aR signaling can activate Rho GTPases, which are involved in cytoskeletal reorganization and cell migration.

These signaling events ultimately result in various cellular responses, including:

* **Chemotaxis and migration:** C5a acts as a potent chemoattractant, attracting immune cells to sites of inflammation.
* **Degranulation:** C5a triggers the release of inflammatory mediators from mast cells and neutrophils.
* **Production of pro-inflammatory cytokines:** C5aR activation stimulates the production of cytokines like TNF-α and IL-6, further amplifying the inflammatory response.
* **Phagocytosis:** C5aR signaling enhances phagocytosis of pathogens by macrophages and neutrophils.
* **Activation of other complement components:** C5aR signaling can promote the activation of other complement components, further amplifying the complement cascade.

C5aR activity plays a crucial role in mediating the inflammatory response to various stimuli, including infections, trauma, and autoimmune diseases. While its activation is essential for immune defense, aberrant or dysregulated C5aR activity can contribute to various inflammatory pathologies. Therefore, targeting C5aR has emerged as a promising strategy for the development of novel therapeutic approaches for inflammatory diseases.'
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Proteins (2)

Compounds (3)