![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on April 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 15, 2001
Revised on December 14, 2001
Accepted on January 8, 2002
1 Department of Cellular and Molecular Medicine and the Howard Hughes Medical Institute, University of California at San Diego, School of Medicine, La Jolla, California 92093-0668
2 Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242
* Corresponding author. E-mail address: semr{at}ucsd.edu.
The Saccharomyces cerevisiae FAB1 gene encodes the sole phosphatidylinositol 3-phosphate [PtdIns(3)P] 5-kinase responsible for synthesis of the polyphosphoinositide PtdIns(3,5)P2. VAC7 encodes a 128 kD transmembrane protein which localizes to vacuolar membranes. Both vac7 and fab1 null mutants have dramatically enlarged vacuoles and cannot grow at elevated temperatures. Additionally, vac7
mutants have nearly undetectable levels of PtdIns(3,5)P2, suggesting that Vac7 functions to regulate Fab1 kinase activity. To test this hypothesis, we isolated a fab1 mutant allele that bypasses the requirement for Vac7 in PtdIns(3,5)P2 production. Expression of this fab1 allele in vac7 mutant cells suppresses the temperature-sensitivity, vacuolar morphology, and PtdIns(3,5)P2 defects normally exhibited by vac7 mutants. We also identified a mutant allele of FIG4, whose gene product contains a Sac1 polyphosphoinositide phosphatase domain, which suppresses vac7 mutant phenotypes. Deletion of FIG4 in vac7 mutant cells suppresses the temperature-sensitivity and vacuolar morphology defects, and dramatically restores PtdIns(3,5)P2 levels. These results suggest that generation of PtdIns(3,5)P2 by the Fab1 lipid kinase is regulated by Vac7, while turnover of PtdIns(3,5)P2 is mediated in part by the Sac1 polyphosphoinositide phosphatase family member, Fig4.
This article has been cited by other articles:
|
|
 |
|
  J. A. Efe, R. J. Botelho, and S. D. Emr Atg18 Regulates Organelle Morphology and Fab1 Kinase Activity Independent of Its Membrane Recruitment by Phosphatidylinositol 3,5-Bisphosphate Mol. Biol. Cell, November 1, 2007; 18(11): 4232 - 4244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, S. N. Zolov, C. Y. Chow, S. G. Slutsky, S. C. Richardson, R. C. Piper, B. Yang, J. J. Nau, R. J. Westrick, S. J. Morrison, et al. Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice PNAS, October 30, 2007; 104(44): 17518 - 17523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sbrissa, O. C. Ikonomov, Z. Fu, T. Ijuin, J. Gruenberg, T. Takenawa, and A. Shisheva Core Protein Machinery for Mammalian Phosphatidylinositol 3,5-Bisphosphate Synthesis and Turnover That Regulates the Progression of Endosomal Transport: NOVEL SAC PHOSPHATASE JOINS THE ArPIKfyve-PIKfyve COMPLEX J. Biol. Chem., August 17, 2007; 282(33): 23878 - 23891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Phelan, S. H. Millson, P. J. Parker, P. W. Piper, and F. T. Cooke Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiae J. Cell Sci., October 15, 2006; 119(20): 4225 - 4234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Duex, J. J. Nau, E. J. Kauffman, and L. S. Weisman Phosphoinositide 5-Phosphatase Fig4p Is Required for both Acute Rise and Subsequent Fall in Stress-Induced Phosphatidylinositol 3,5-Bisphosphate Levels. Eukaryot. Cell, April 1, 2006; 5(4): 723 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Voronkova, N. Kacherovsky, C. Tachibana, D. Yu, and E. T. Young Snf1-Dependent and Snf1-Independent Pathways of Constitutive ADH2 Expression in Saccharomyces cerevisiae Genetics, April 1, 2006; 172(4): 2123 - 2138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Duex, F. Tang, and L. S. Weisman The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover J. Cell Biol., February 27, 2006; 172(5): 693 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Parrish, C. J. Stefan, and S. D. Emr PtdIns(3)P accumulation in triple lipid-phosphatase-deletion mutants triggers lethal hyperactivation of the Rho1p/Pkc1p cell-integrity MAP kinase pathway J. Cell Sci., December 1, 2005; 118(23): 5589 - 5601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sbrissa, O. C. Ikonomov, J. Strakova, R. Dondapati, K. Mlak, R. Deeb, R. Silver, and A. Shisheva A Mammalian Ortholog of Saccharomyces cerevisiae Vac14 That Associates with and Up-Regulates PIKfyve Phosphoinositide 5-Kinase Activity Mol. Cell. Biol., December 1, 2004; 24(23): 10437 - 10447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Parrish, C. J. Stefan, and S. D. Emr Essential Role for the Myotubularin-related Phosphatase Ymr1p and the Synaptojanin-like Phosphatases Sjl2p and Sjl3p in Regulation of Phosphatidylinositol 3-Phosphate in Yeast Mol. Biol. Cell, August 1, 2004; 15(8): 3567 - 3579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Roth Phosphoinositides in Constitutive Membrane Traffic Physiol Rev, July 1, 2004; 84(3): 699 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Hernandez, K. Hueffer, M. R. Wenk, and J. E. Galan Salmonella Modulates Vesicular Traffic by Altering Phosphoinositide Metabolism Science, June 18, 2004; 304(5678): 1805 - 1807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Nikko, A.-M. Marini, and B. Andre Permease Recycling and Ubiquitination Status Reveal a Particular Role for Bro1 in the Multivesicular Body Pathway J. Biol. Chem., December 12, 2003; 278(50): 50732 - 50743. [Abstract] [Full Text] [PDF]
|
|
