Switch-associated protein 70 (SWAP70) is a protein that binds to actin and participates in various cellular processes such as cytoskeleton remodeling, signal transduction, and membrane dynamic changes. Recent studies have shown that SWAP70 plays a key role in phagocytosis, especially in the formation and maturation of phagosomes. Phagocytosis is an evolutionarily conserved mechanism by which immune cells take up foreign particles, such as microbial pathogens and tumor cells, and degrade them.
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Key Mechanisms of SWAP70 on The Phagosome Surface
Recruitment and Localization
Activation and recruitment of Rho family small GTPases (such as Rac1), and its own PH domain (pleckstrin homology domain) ability to bind to phospholipids.
Regulating Actin Polymerization
SWAP70 is an actin-binding protein that stabilizes the F-actin structure. Recruitment and activation of the WAVE/Arp2/3 complex promotes actin branch polymerization and forms an actin cup that supports phagosomes to encapsulate pathogens or particles.
Regulating the Activity of Small GTPase Rac
SWAP70 regulates the activity state of Rac1 through its GEF-like domain. After activation, Rac1 promotes actin remodeling and helps the formation and closure of phagosomes.
Regulating Phagosome Maturation
After phagosome formation, SWAP70 participates in regulating the fusion process between phagosome and endosome/lysosome. It promotes the transport and acidification of phagosome by regulating the dynamics of actin on the membrane, and may cooperate with Rab GTPase (such as Rab5, Rab7) to promote maturation.
Fig1. SWAP70 is involved in important phagocytosis (Baranov, M., et al. 2016).
Physiological Activity of SWAP70
Actin Cytoskeleton Regulation
SWAP70 can directly bind to F-actin (fibrous actin) and regulate its structure and dynamic changes. It plays an important role in cell migration, membrane ruffle formation, and pseudopodia formation of immune cells.
Regulating the Activity of Small GTPases
SWAP70 has a regulatory effect on Rho family small GTPases (especially Rac1) through its domain. It promotes the activation of Rac1, thereby regulating downstream actin remodeling and cell migration. This function is particularly important for the directional movement and endocytosis of immune cells such as macrophages and dendritic cells.
Participate in Endocytosis and Phagocytosis
SWAP70 is recruited to newly formed phagosomes to regulate the formation of phagocytic cups and phagosome maturation. It assists in the polymerization of actin during phagocytosis and regulates the membrane remodeling and content degradation of phagosomes.
Regulate Cell Polarity and Migration
SWAP70 plays an important role in the establishment and maintenance of cell polarity. Through its regulation of the actin cytoskeleton and Rac1, SWAP70 can affect the direction and speed of cell migration. It helps maintain tissue structure in cell types such as epithelial cells and neurons.
Regulate Immune Cell Function
In B cell activation and dendritic cell maturation, SWAP70 is essential for signal transduction and cell morphological changes. For example, after B cells are stimulated by antigens, SWAP70 assists in cytoskeleton remodeling and promotes the formation of immune synapses. In dendritic cells, SWAP70 helps form pseudopodia and enhances their antigen uptake and migration capabilities.
Participation in Signal Transduction Pathways
SWAP70 can act as an adaptor protein to connect membrane receptor signals with dynamic changes in the cytoskeleton. For example, it participates in the PI3K/Akt pathway, the Rac1 signaling pathway, the antigen receptor signaling pathway.
The Important Role of SWAP70 on The Phagosome Surface
The key mechanisms of SWAP70 on the phagosome surface can be summarized as follows:
| Mechanism of action |
Specific function description |
| Site recruitment |
Recognizes phospholipids through the PH domain and locates in the phagosome membrane |
| Rac1 activation |
Promotes the activity of small GTPases and enhances signal transduction |
| Phagosome maturation regulation |
Assists fusion with lysosomes and promotes degradation of their contents |
References
- Shinohara, M., et al. SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling. Nature. 2002, 416(6882): 759-763.
- Baranov, M., et al. SWAP70 organizes the actin cytoskeleton and is essential for phagocytosis. Cell reports. 2016, 17(6): 1518-1531.
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