Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E08-04-0405 on July 23, 2008

Vol. 19, Issue 10, 4273-4286, October 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E08-04-0405v1
19/10/4273    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Botelho, R. J.
Right arrow Articles by Emr, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Botelho, R. J.
Right arrow Articles by Emr, S. D.

Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

Roberto J. Botelho*, Jem A. Efe{dagger},{ddagger}, David Teis*, and Scott D. Emr*

*Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, 14853; and {dagger}Division of Biology, University of California, San Diego, La Jolla, CA 92093-0668

Submitted April 21, 2008; Revised July 11, 2008; Accepted July 15, 2008
Monitoring Editor: John York

Phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] regulates several vacuolar functions, including acidification, morphology, and membrane traffic. The lipid kinase Fab1 converts phosphatidylinositol-3-phosphate [PtdIns(3)P] to PtdIns(3,5)P2. PtdIns(3,5)P2 levels are controlled by the adaptor-like protein Vac14 and the Fig4 PtdIns(3,5)P2-specific 5-phosphatase. Interestingly, Vac14 and Fig4 serve a dual function: they are both implicated in the synthesis and turnover of PtdIns(3,5)P2 by an unknown mechanism. We now show that Fab1, through its chaperonin-like domain, binds to Vac14 and Fig4 and forms a vacuole-associated signaling complex. The Fab1 complex is tethered to the vacuole via an interaction between the FYVE domain in Fab1 and PtdIns(3)P on the vacuole. Moreover, Vac14 and Fig4 bind to each other directly and are mutually dependent for interaction with the Fab1 kinase. Our observations identify a protein complex that incorporates the antagonizing Fab1 lipid kinase and Fig4 lipid phosphatase into a common functional unit. We propose a model explaining the dual roles of Vac14 and Fig4 in the synthesis and turnover of PtdIns(3,5)P2.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-04-0405) on July 23, 2008.

{ddagger} Present address: The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037.

Address correspondence to: Scott D. Emr (sde26{at}cornell.edu)

Abbreviations used: CCR, conserved cysteine-rich domain; coIP, coimmunoprecipitation; PtdIns(3,5)P2, phosphatidylinositol-3,5-bisphosphate; HPLC, high-performance liquid chromatography; IP, immunoprecipitation; PtdInsP, phosphoinositide; V/C, vacuole-to-cytosol fluorescence ratio.




This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
P. W. Majerus and J. D. York
Phosphoinositide phosphatases and disease
J. Lipid Res., April 1, 2009; 50(Supplement): S249 - S254.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.