- THIS ARTICLE
- Full Text
- Full Text (PDF)
-
All Versions of this Article:
genetics.104.034983v1
169/2/539 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Weisman, R.
- Articles by Kupiec, M.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Weisman, R.
- Articles by Kupiec, M.
Originally published as Genetics Published Articles Ahead of Print on September 30, 2004.
Genetics, Vol. 169, 539-550, February 2005, Copyright © 2005
doi:10.1534/genetics.104.034983
Regulation of Leucine Uptake by tor1+ in Schizosaccharomyces pombe Is Sensitive to Rapamycin
Ronit Weisman1, Irina Roitburg, Tal Nahari and Martin Kupiec
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel
1 Corresponding author: Department of Molecular Microbiology and Biotechnology, Green Bldg., Room 211, Tel-Aviv University, Ramat Aviv, 69978 Tel-Aviv, Israel.
E-mail: ronitt{at}post.tau.ac.il
TOR protein kinases are key regulators of cell growth in eukaryotes. TOR is also known as the target protein for the immunosuppressive and potentially anticancer drug rapamycin. The fission yeast Schizosaccharomyces pombe has two TOR homologs. tor1+ is required under starvation and a variety of stresses, while tor2+ is an essential gene. Surprisingly, to date no rapamycin-sensitive TOR-dependent function has been identified in S. pombe. Herein, we show that S. pombe auxotrophs, in particular leucine auxotrophs, are sensitive to rapamycin. This sensitivity is suppressed by deletion of the S. pombe FKBP12 or by introducing a rapamycin-binding defective tor1 allele, suggesting that rapamycin inhibits a tor1p-dependent function. Sensitivity of leucine auxotrophs to rapamycin is observed when ammonia is used as the nitrogen source and can be suppressed by its replacement with proline. Consistently, using radioactive labeled leucine, we show that cells treated with rapamycin or disrupted for tor1+ are defective in leucine uptake when the nitrogen source is ammonia but not proline. Recently, it has been reported that tsc1+ and tsc2+, the S. pombe homologs for the mammalian TSC1 and TSC2, are also defective in leucine uptake. TSC1 and TSC2 may antagonize TOR signaling in mammalian cells and Drosophila. We show that reduction of leucine uptake in tor1 mutants is correlated with decreased expression of three putative amino acid permeases that are also downregulated in tsc1 or tsc2. These findings suggest a possible mechanism for regulation of leucine uptake by tor1p and indicate that tor1p, as well as tsc1p and tsc2p, positively regulates leucine uptake in S. pombe.
This article has been cited by other articles:
 |
|
 |
|
  T. Hayashi, M. Hatanaka, K. Nagao, Y. Nakaseko, J. Kanoh, A. Kokubu, M. Ebe, and M. Yanagida Rapamycin sensitivity of the Schizosaccharomyces pombe tor2 mutant and organization of two highly phosphorylated TOR complexes by specific and common subunits. Genes Cells, December 1, 2007; 12(12): 1357 - 1370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. van Slegtenhorst, D. Khabibullin, T. R. Hartman, E. Nicolas, W. D. Kruger, and E. P. Henske The Birt-Hogg-Dube and Tuberous Sclerosis Complex Homologs Have Opposing Roles in Amino Acid Homeostasis in Schizosaccharomyces pombe J. Biol. Chem., August 24, 2007; 282(34): 24583 - 24590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Zurita-Martinez, R. Puria, X. Pan, J. D. Boeke, and M. E. Cardenas Efficient Tor Signaling Requires a Functional Class C Vps Protein Complex in Saccharomyces cerevisiae Genetics, August 1, 2007; 176(4): 2139 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Roos, N. Jansson, I. Palmberg, K. Saljo, T. L. Powell, and T. Jansson Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth J. Physiol., July 1, 2007; 582(1): 449 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsuo, Y. Otsubo, J. Urano, F. Tamanoi, and M. Yamamoto Loss of the TOR Kinase Tor2 Mimics Nitrogen Starvation and Activates the Sexual Development Pathway in Fission Yeast Mol. Cell. Biol., April 15, 2007; 27(8): 3154 - 3164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weisman, I. Roitburg, M. Schonbrun, R. Harari, and M. Kupiec Opposite Effects of Tor1 and Tor2 on Nitrogen Starvation Responses in Fission Yeast Genetics, March 1, 2007; 175(3): 1153 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Urano, T. Sato, T. Matsuo, Y. Otsubo, M. Yamamoto, and F. Tamanoi Point mutations in TOR confer Rheb-independent growth in fission yeast and nutrient-independent mammalian TOR signaling in mammalian cells PNAS, February 27, 2007; 104(9): 3514 - 3519. [Abstract] [Full Text] [PDF]
|
|