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Published 1 October 2001. doi:10.1083/jcb.200107069
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© The Rockefeller University Press, 0021-9525/2001/10/19 $5.00
The Journal of Cell Biology, Volume 155, Number 1, October 1, 2001 19-26

Report

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



Otilia V. Vieira1,2, Roberto J. Botelho1, Lucia Rameh3, Saskia M. Brachmann3,4, Tsuyoshi Matsuo3, Howard W. Davidson5, Alan Schreiber6, Jonathan M. Backer7, Lewis C. Cantley3 and Sergio Grinstein1

1 Cell Biology Program, Hospital for Sick Children and Department of Biochemistry, University of Toronto, Ontario M5G 1X8, Canada
2 Center for Neurosciences, University of Coimbra, 3000 Coimbra, Portugal
3 Divison of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115
4 Freie Universitaet Berlin, Institut fuer Biochemie, 14195 Berlin, Germany
5 Wellcome Trust Center for Molecular Mechanisms of Disease, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 2QQ, UK
6 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
7 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10032

Address correspondence to Sergio Grinstein, Division of Cell Biology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. Tel.: (416) 813-5727. Fax: (416) 813-5028. E-mail: sga{at}sickkids.on.ca

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.

Key Words: phagocytosis; phosphatidylinositol; FYVE domain; EEA1; lysosomes


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