This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tabuchi, M.
Right arrow Articles by Emr, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tabuchi, M.
Right arrow Articles by Emr, S. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2006, p. 5861-5875, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.02403-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Phosphatidylinositol 4,5-Biphosphate and TORC2 Binding Proteins Slm1 and Slm2 Function in Sphingolipid Regulation{dagger}

Mitsuaki Tabuchi ,1,{ddagger},§ Anjon Audhya,1,§,¶ Ainslie B. Parsons,2,3 Charles Boone,2,3 and Scott D. Emr1*

Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla, California 92093-0668,1 Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada,2 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada3

Received 16 December 2005/ Returned for modification 6 February 2006/ Accepted 8 May 2006

The Stt4 phosphatidylinositol 4-kinase has been shown to generate a pool of phosphatidylinositol 4-phosphate (PI4P) at the plasma membrane, critical for actin cytoskeleton organization and cell viability. To further understand the essential role of Stt4-mediated PI4P production, we performed a genetic screen using the stt4ts mutation to identify candidate regulators and effectors of PI4P. From this analysis, we identified several genes that have been previously implicated in lipid metabolism. In particular, we observed synthetic lethality when both sphingolipid and PI4P synthesis were modestly diminished. Consistent with these data, we show that the previously characterized phosphoinositide effectors, Slm1 and Slm2, which regulate actin organization, are also necessary for normal sphingolipid metabolism, at least in part through regulation of the calcium/calmodulin-dependent phosphatase calcineurin, which binds directly to both proteins. Additionally, we identify Isc1, an inositol phosphosphingolipid phospholipase C, as an additional target of Slm1 and Slm2 negative regulation. Together, our data suggest that Slm1 and Slm2 define a molecular link between phosphoinositide and sphingolipid signaling and thereby regulate actin cytoskeleton organization.

* Corresponding author. Mailing address: Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0668. Phone: (858) 534-6462. Fax: (858) 534-6414. E-mail: semr{at}ucsd.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Molecular Genetics, Field of Developmental Medicine, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

§ These authors contributed equally to this work.

Present address: Ludwig Institute for Cancer Research, La Jolla, CA 92093.

Molecular and Cellular Biology, August 2006, p. 5861-5875, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.02403-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Frohlich, F., Moreira, K., Aguilar, P. S., Hubner, N. C., Mann, M., Walter, P., Walther, T. C. (2009). A genome-wide screen for genes affecting eisosomes reveals Nce102 function in sphingolipid signaling. JCB 185: 1227-1242 [Abstract] [Full Text]  
  • Brice, S. E., Alford, C. W., Cowart, L. A. (2009). Modulation of Sphingolipid Metabolism by the Phosphatidylinositol-4-phosphate Phosphatase Sac1p through Regulation of Phosphatidylinositol in Saccharomyces cerevisiae. J. Biol. Chem. 284: 7588-7596 [Abstract] [Full Text]  
  • Berchtold, D., Walther, T. C. (2009). TORC2 Plasma Membrane Localization Is Essential for Cell Viability and Restricted to a Distinct Domain. Mol. Biol. Cell 20: 1565-1575 [Abstract] [Full Text]  
  • Soukas, A. A., Kane, E. A., Carr, C. E., Melo, J. A., Ruvkun, G. (2009). Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes Dev. 23: 496-511 [Abstract] [Full Text]  
  • Baird, D., Stefan, C., Audhya, A., Weys, S., Emr, S. D. (2008). Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3. JCB 183: 1061-1074 [Abstract] [Full Text]  
  • Dudgeon, D. D., Zhang, N., Ositelu, O. O., Kim, H., Cunningham, K. W. (2008). Nonapoptotic Death of Saccharomyces cerevisiae Cells That Is Stimulated by Hsp90 and Inhibited by Calcineurin and Cmk2 in Response to Endoplasmic Reticulum Stresses. Eukaryot Cell 7: 2037-2051 [Abstract] [Full Text]  
  • Mousley, C. J., Tyeryar, K., Ile, K. E., Schaaf, G., Brost, R. L., Boone, C., Guan, X., Wenk, M. R., Bankaitis, V. A. (2008). Trans-Golgi Network and Endosome Dynamics Connect Ceramide Homeostasis with Regulation of the Unfolded Protein Response and TOR Signaling in Yeast. Mol. Biol. Cell 19: 4785-4803 [Abstract] [Full Text]  
  • Dickson, R. C. (2008). Thematic Review Series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast. J. Lipid Res. 49: 909-921 [Abstract] [Full Text]  
  • Matmati, N., Hannun, Y. A. (2008). Thematic Review Series: Sphingolipids. ISC1 (inositol phosphosphingolipid-phospholipase C), the yeast homologue of neutral sphingomyelinases. J. Lipid Res. 49: 922-928 [Abstract] [Full Text]  
  • Luo, G., Gruhler, A., Liu, Y., Jensen, O. N., Dickson, R. C. (2008). The Sphingolipid Long-chain Base-Pkh1/2-Ypk1/2 Signaling Pathway Regulates Eisosome Assembly and Turnover. J. Biol. Chem. 283: 10433-10444 [Abstract] [Full Text]  
  • Shen, C., Lancaster, C. S., Shi, B., Guo, H., Thimmaiah, P., Bjornsti, M.-A. (2007). TOR Signaling Is a Determinant of Cell Survival in Response to DNA Damage. Mol. Cell. Biol. 27: 7007-7017 [Abstract] [Full Text]  
  • Aronova, S., Wedaman, K., Anderson, S., Yates, J. III, Powers, T. (2007). Probing the Membrane Environment of the TOR Kinases Reveals Functional Interactions between TORC1, Actin, and Membrane Trafficking in Saccharomyces cerevisiae. Mol. Biol. Cell 18: 2779-2794 [Abstract] [Full Text]  
  • Daquinag, A., Fadri, M., Jung, S. Y., Qin, J., Kunz, J. (2007). The Yeast PH Domain Proteins Slm1 and Slm2 Are Targets of Sphingolipid Signaling during the Response to Heat Stress. Mol. Cell. Biol. 27: 633-650 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»