Involvement of heterotrimeric G proteins in phagocytosis and recycling from the phagosomal compartment.
Phagocytosis is a receptor-mediated process by which specialized cell types engulf large extracellular particles. Phagosome maturation involves a series of intracellular membrane fusion and budding events resulting in the delivery of particles to compartments enriched in lysosomal hydrolases where they are digested. Substantial amounts of plasma membrane and many phagosomal proteins, such as receptors, rapidly recycle to the plasma membrane following phagosome formation. Despite the importance of this recycling pathway in phagosome maturation and in the retrieval of immunogenic peptides from phagosomes, the molecular machinery involved is largely unknown. To assess the participation of GTPases in phagocytosis and recycling from phagosomes we used aluminum fluoride (AIF(-)(4)), which activates the GDP-bound form of stimulatory and inhibitory trimeric G proteins. AlF(-)(4) inhibited both the uptake to and the recycling from the phagosomal compartment. Cholera toxin, which activates Galphas, and pertussis toxin, which uncouples Gi and Go from receptors, were effective inhibitors of phagocytosis. However, both toxins stimulated recycling from phagosomes. These results suggest that more than one GTP-binding protein participates either directly or indirectly not only in phagocytosis, but also in maturation and recycling from phagosomes, and thereby assign a role for heterotrimeric G proteins in controlling traffic through the phagocytic pathway.
Damiani
M T
MT
Instituto de Histología y Embriología, Universidad Nacional de Cuyo-CONICET, Mendoza, 5500, Argentina.
Colombo
M I
MI
D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins; D005459:Fluorides; C032311:aluminum fluoride