JCB logo
Direct PCR from Finnzymes
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 1 October 2001. doi:10.1083/jcb.200107069
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vieira, O. V.
Right arrow Articles by Grinstein, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vieira, O. V.
Right arrow Articles by Grinstein, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© 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


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents