Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation.

Vieira OV, Botelho RJ, Rameh L, Brachmann SM, Matsuo T, Davidson HW, Schreiber A, Backer JM, Cantley LC, Grinstein S
J Cell Biol. 2001 155 (1): 19-25

PMID: 11581283 · PMCID: PMC2150784 · DOI:10.1083/jcb.200107069

Phagosomes acquire their microbicidal properties by fusion with lysosomes. Products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for phagosome formation, but their role in maturation is unknown. Using chimeric fluorescent proteins encoding tandem FYVE domains, we found that phosphatidylinositol 3-phosphate (PI[3]P) accumulates greatly but transiently on the phagosomal membrane. Unlike the 3'-phosphoinositides generated by class I PI 3-kinases which are evident in the nascent phagosomal cup, PI(3)P is only detectable after the phagosome has sealed. The class III PI 3-kinase VPS34 was found to be responsible for PI(3)P synthesis and essential for phagolysosome formation. In contrast, selective ablation of class I PI 3-kinase revealed that optimal phagocytosis, but not maturation, requires this type of enzyme. These results highlight the differential functional role of the two families of kinases, and raise the possibility that PI(3)P production by VPS34 may be targeted during the maturation arrest induced by some intracellular parasites.

MeSH Terms (20)

Androstadienes Animals Cells, Cultured Enzyme Inhibitors Fibroblasts Genes, Reporter Humans Immunoglobulin G Isoenzymes Lysosomes Macrophages Mice Mice, Knockout Microinjections Phagocytosis Phagosomes Phosphatidylinositol 3-Kinases Protein Structure, Tertiary Recombinant Fusion Proteins Wortmannin

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