ArticleMolecular and cellular biology2003
Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 338 citations in OpenAlex.
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- RAB5c orchestrates LC3-associated phagocytosis to promote microbicidal function of macrophages.Science advances · 2026Article
- PIKfyve is required for efficient phagosomal Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes.Journal of cell science · 2026Article
- Modulation of immune cells and metabolic reprogramming in efferocytosis.Cell death & disease · 2026Review
- More Than a Cleanup Crew: The Expanding Biology of Efferocytosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Targeting efferocytosis for tissue regeneration: From microenvironment reprogramming to clinical translation.Theranostics · 2026Review
- The CCC complex directs phagosomal maturation and bactericidal activity in macrophages through PI(3)P regulation.bioRxiv : the preprint server for biology · 2025Article
- Phagocytosis at a glance.Journal of cell science · 2025Review
- RAB5c controls the assembly of non-canonical autophagy machinery to promote phagosome maturation and microbicidal function of macrophages.bioRxiv : the preprint server for biology · 2025Article
- Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles.Nature communications · 2025Article
- Bactericidal ability of target acidic phospholipids and phagocytosis of CDC42 GTPase-mediated cytoskeletal rearrangement underlie functional conservation of CXCL12 in vertebrates.Science China. Life sciences · 2024Article
- The frequency of CD38Nature communications · 2024Article
- CD38+ Alveolar macrophages mediate early control of M. tuberculosis proliferation in the lung.Research square · 2024Article
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- Efferocytosis: the resolution of inflammation in cardiovascular and cerebrovascular disease.Frontiers in immunology · 2024Review
- Phagocytosis.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Transcriptomic insights into the shift of trophic strategies in mixotrophic dinoflagellateISME communications · 2024Article
- Activated Src kinase promotes cell cannibalism in Drosophila.The Journal of cell biology · 2023Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phagosomal biogenesis is central for microbial killing and antigen presentation by leukocytes. However, the molecular mechanisms governing phagosome maturation are poorly understood. We analyzed the role and site of action of phosphatidylinositol 3-kinases (PI3K) and of Rab GTPases in maturation using both professional and engineered phagocytes. Rab5, which is recruited rapidly and transiently to the phagosome, was found to be essential for the recruitment of Rab7 and for progression to phagolysosomes. Similarly, functional PI3K is required for successful maturation. Remarkably, inhibition of PI3K did not preclude Rab5 recruitment to phagosomes but instead enhanced and prolonged it. Moreover, in the presence of PI3K inhibitors Rab5 was found to be active, as deduced from measurements of early endosome antigen 1 binding and by photobleaching recovery determinations. Though their ability to fuse with late endosomes and lysosomes was virtually eliminated by wortmannin, phagosomes nevertheless recruited a sizable amount of Rab7. Moreover, Rab7 recruited to phagosomes in the presence of PI3K antagonists retained the ability to bind its effector, Rab7-interacting lysosomal protein, suggesting that it is functionally active. These findings imply that (i) dissociation of Rab5 from phagosomes requires products of PI3K, (ii) PI3K-dependent effectors of Rab5 are not essential for the recruitment of Rab7 by phagosomes, and (iii) recruitment and activation of Rab7 are insufficient to induce fusion of phagosomes with late endosomes and lysosomes. Accordingly, transfection of constitutively active Rab7 did not bypass the block of phagolysosome formation exerted by wortmannin. We propose that Rab5 activates both PI3K-dependent and PI3K-independent effectors that act in parallel to promote phagosome maturation.
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