| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print June 21, 2004
Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198
Corresponding Author: hirabaya{at}postman.riken.go.jp
Glucosylceramide synthase (GlcT-1) catalyzes the formation of glucosylceramide (GlcCer), the core structure of major glycosphingolipids (GSLs), from ceramide and UDP-glucose. Ceramide and its metabolites, such as sphingosine-1-phosphate, are now known to be an important mediator of apoptosis and cell survival. Recently, we have shown that GlcT-1 functions to regulate intracellular ceramide levels via glycosylation of ceramide. In this study, we employ the fruit fly Drosophila melanogaster as a model system for understanding the in vivo roles of GlcT-1. We isolated and characterized a GlcT-1 homologue (DGlcT-1) from Drosophila. When DGlcT-1 was expressed in GM-95 cells deficient in GSLs (due to the absence of GlcT-1 activity), these cell regained the ability to synthesize GSLs. Northern blot and in situ hybridization analyses revealed that the expression of DGlcT-1 mRNA was ubiquitous throughout development, suggesting that DGlcT-1 is important for development and differentiation. Indeed, RNA interference experiments demonstrated that the loss of GlcT-1 function enhances of apoptotic cell death. Conversely, targeted expression of GlcT-1 partially rescued cell death caused by the proapoptotic factors Reaper and Grim, suggesting that ceramide generation might be one signal pathway that executes the cell death program. We also found that GlcT-1 localized not only in the Golgi apparatus but also in the perinuclear endoplasmic reticulum, providing the first visual evidence of GlcT-1 in membranes. These results indicate that GlcT-1 might down-regulate ceramide generated in these membranes.
J. Biol. Chem, 10.1074/jbc.M400444200
Submitted on January 15, 2004
Revised on May 24, 2004
Accepted on June 21, 2004
Drosophila glucosylceramide synthase: A negative regulator of cell death mediated by proapoptotic factors
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Fyrst, X. Zhang, D. R. Herr, H. S. Byun, R. Bittman, V. H. Phan, G. L. Harris, and J. D. Saba Identification and characterization by electrospray mass spectrometry of endogenous Drosophila sphingadienes J. Lipid Res., March 1, 2008; 49(3): 597 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Le Stunff, P. Giussani, M. Maceyka, S. Lepine, S. Milstien, and S. Spiegel Recycling of Sphingosine Is Regulated by the Concerted Actions of Sphingosine-1-phosphate Phosphohydrolase 1 and Sphingosine Kinase 2 J. Biol. Chem., November 23, 2007; 282(47): 34372 - 34380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hayashi, N. Okino, Y. Kakuta, T. Shikanai, M. Tani, H. Narimatsu, and M. Ito Klotho-related Protein Is a Novel Cytosolic Neutral beta-Glycosylceramidase J. Biol. Chem., October 19, 2007; 282(42): 30889 - 30900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Levine A lipid transfer protein that transfers lipid J. Cell Biol., October 8, 2007; 179(1): 11 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Halter, S. Neumann, S. M. van Dijk, J. Wolthoorn, A. M. de Maziere, O. V. Vieira, P. Mattjus, J. Klumperman, G. van Meer, and H. Sprong Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis J. Cell Biol., October 8, 2007; 179(1): 101 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Fuller, T. Schwientek, H. H. Wandall, J. W. Pedersen, H. Clausen, and S. B. Levery Structure elucidation of neutral, di-, tri-, and tetraglycosylceramides from High Five cells: identification of a novel (non-arthro-series) glycosphingolipid pathway Glycobiology, December 1, 2005; 15(12): 1286 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Holzl, M. Leipelt, C. Ott, U. Zahringer, B. Lindner, D. Warnecke, and E. Heinz Processive lipid galactosyl/glucosyltransferases from Agrobacterium tumefaciens and Mesorhizobium loti display multiple specificities Glycobiology, September 1, 2005; 15(9): 874 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Wandall, S. Pizette, J. W. Pedersen, H. Eichert, S. B. Levery, U. Mandel, S. M. Cohen, and H. Clausen Egghead and Brainiac Are Essential for Glycosphingolipid Biosynthesis in Vivo J. Biol. Chem., February 11, 2005; 280(6): 4858 - 4863. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
