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doi:10.1534/genetics.104.034983
A more recent version of this article appeared on February 1, 2005.
REGULAR RESEARCH PAPERS |
Regulation of leucine uptake by tor1+in Schizosaccharomyces pombe is sensitive to rapamycin
Ronit Weisman 1*, Irina Roitburg 2, Tal Nahari 2 and Martin Kupiec 2
1 Tel-Aviv University
2 Tel Aviv University
* To whom correspondence should be addressed. E-mail: ronitt{at}post.tau.ac.il.
Submitted on August 13, 2004
Revised on September 16, 2004
Accepted on 27 September 2004
TOR protein kinases are key regulators of cell growth in eukaryotes. TOR is also known as the target protein for the immunosuppressive and potentially anti-cancerous drug rapamycin. The fission yeast, Schizosaccharomyces pombe, has two TOR homologues. 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 homologues 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 down regulated 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 regulate leucine uptake in S. pombe.
Key Words: Schizosaccharomyces pombe, rapamycin, tor1/tor2
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