Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis

Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis

2000 February 11; 287(5455): 1037–1040 | Guy Servant, Orion D. Weiner, Paul Herzmark, Tamás Balla, John W. Sedat, and Henry R. Bourne
The study investigates the polarization of chemoattractant receptor signaling during neutrophil chemotaxis. The authors used a fluorescent probe, PHAKT-GFP (pleckstrin homology domain of the AKT protein kinase tagged with green fluorescent protein), to track intracellular signaling gradients in neutrophils. Upon exposure to chemoattractants, PHAKT-GFP was selectively recruited to the cell's leading edge, indicating a steep internal signaling gradient. This recruitment was inhibited by toxin-B from *Clostridium difficile*, suggesting the involvement of Rho guanosine triphosphatases (Rho GTPases). The study also found that actin polymerization was not necessary for PHAKT-GFP translocation, as latrunculin-B, which sequesters monomeric actin, did not affect this process. Additionally, the authors demonstrated that Rho GTPases and phosphatidylinositol 3-kinase (PI3K) are required for PHAKT-GFP translocation. The results suggest that the amplification of the external signaling gradient into an internal signal involves an intermediate pathway dependent on Rho GTPases and PI3K products. The study also speculates that Cdc42 may play a crucial role in determining the asymmetry of the chemoattractant response.The study investigates the polarization of chemoattractant receptor signaling during neutrophil chemotaxis. The authors used a fluorescent probe, PHAKT-GFP (pleckstrin homology domain of the AKT protein kinase tagged with green fluorescent protein), to track intracellular signaling gradients in neutrophils. Upon exposure to chemoattractants, PHAKT-GFP was selectively recruited to the cell's leading edge, indicating a steep internal signaling gradient. This recruitment was inhibited by toxin-B from *Clostridium difficile*, suggesting the involvement of Rho guanosine triphosphatases (Rho GTPases). The study also found that actin polymerization was not necessary for PHAKT-GFP translocation, as latrunculin-B, which sequesters monomeric actin, did not affect this process. Additionally, the authors demonstrated that Rho GTPases and phosphatidylinositol 3-kinase (PI3K) are required for PHAKT-GFP translocation. The results suggest that the amplification of the external signaling gradient into an internal signal involves an intermediate pathway dependent on Rho GTPases and PI3K products. The study also speculates that Cdc42 may play a crucial role in determining the asymmetry of the chemoattractant response.
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[slides] Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. | StudySpace