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

Otilia V. Vieira, Roberto J. Botelho, Lucia Rameh, Saskia M. Brachmann, Tsuyoshi Matsuo, Howard W. Davidson, Alan Schreiber, Jonathan M. Backer, Lewis C. Cantley, Sergio Grinstein

Research output: Contribution to journalArticle

382 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19-25
Number of pages7
JournalJournal of Cell Biology
Volume155
Issue number1
DOIs
StatePublished - Oct 1 2001

Keywords

  • EEA1
  • FYVE domain
  • Lysosomes
  • Phagocytosis
  • Phosphatidylinositol

ASJC Scopus subject areas

  • Cell Biology

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    Vieira, O. V., Botelho, R. J., Rameh, L., Brachmann, S. M., Matsuo, T., Davidson, H. W., Schreiber, A., Backer, J. M., Cantley, L. C., & Grinstein, S. (2001). Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation. Journal of Cell Biology, 155(1), 19-25. https://doi.org/10.1083/jcb.200107069