Rab-Family GTPase regulates TOR complex 2 signaling in fission yeast

Hisashi Tatebe, Susumu Morigasaki, Shinichi Murayama, Cui Tracy Zeng, Kazuhiro Shiozaki

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Abstract

Background: From yeast to human, TOR (target of rapamycin) kinase plays pivotal roles in coupling extracellular stimuli to cell growth and metabolism. TOR kinase functions in two distinct protein complexes, TOR complex 1 (TORC1) and 2 (TORC2), which phosphorylate and activate different AGC-family protein kinases. TORC1 is controlled by the small GTPase Rheb, but little is known about TORC2 regulators. Results: We have identified the Ryh1 GTPase, a human Rab6 ortholog, as an activator of TORC2 signaling in the fission yeast Schizosaccharomyces pombe. Mutational inactivation of Ryh1 or its guanine nucleotide exchange factor compromises the TORC2-dependent phosphorylation of the AGC-family Gad8 kinase. In addition, the effector domain of Ryh1 is important for its physical interaction with TORC2 and for stimulation of TORC2 signaling. Thus, GTP-bound Ryh1 is likely to be the active form stimulatory to TORC2-Gad8 signaling. Consistently, expression of the GTP-locked mutant Ryh1 is sufficient to promote interaction between TORC2 and Gad8 and to induce Gad8 hyperphosphorylation. The loss of functional Ryh1, TORC2, or Gad8 brings about similar vacuolar fragmentation and stress sensitivity, further corroborating their involvement in a common cellular process. Human Rab6 can substitute Ryh1 in S. pombe, and therefore Rab6 may be a potential activator of TORC2 in mammals. Conclusions: In its GTP-bound form, Ryh1, an evolutionarily conserved Rab GTPase, activates TORC2 signaling to the AGC kinase Gad8. The Ryh1 GTPase and the TORC2-Gad8 pathway are required for vacuolar integrity and cellular stress resistance in S. pombe.

Original languageEnglish (US)
Pages (from-to)1975-1982
Number of pages8
JournalCurrent Biology
Volume20
Issue number22
DOIs
StatePublished - Nov 23 2010

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rab GTP-Binding Proteins
Schizosaccharomyces
Schizosaccharomyces pombe
GTP Phosphohydrolases
guanosinetriphosphatase
Yeast
phosphotransferases (kinases)
Phosphotransferases
protein kinases
stress tolerance
Guanosine Triphosphate
cell growth
phosphorylation
inactivation
mammals
yeasts
Sirolimus
mutants
metabolism
mechanistic target of rapamycin complex 1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tatebe, H., Morigasaki, S., Murayama, S., Zeng, C. T., & Shiozaki, K. (2010). Rab-Family GTPase regulates TOR complex 2 signaling in fission yeast. Current Biology, 20(22), 1975-1982. https://doi.org/10.1016/j.cub.2010.10.026

Rab-Family GTPase regulates TOR complex 2 signaling in fission yeast. / Tatebe, Hisashi; Morigasaki, Susumu; Murayama, Shinichi; Zeng, Cui Tracy; Shiozaki, Kazuhiro.

In: Current Biology, Vol. 20, No. 22, 23.11.2010, p. 1975-1982.

Research output: Contribution to journalArticle

Tatebe, H, Morigasaki, S, Murayama, S, Zeng, CT & Shiozaki, K 2010, 'Rab-Family GTPase regulates TOR complex 2 signaling in fission yeast', Current Biology, vol. 20, no. 22, pp. 1975-1982. https://doi.org/10.1016/j.cub.2010.10.026
Tatebe H, Morigasaki S, Murayama S, Zeng CT, Shiozaki K. Rab-Family GTPase regulates TOR complex 2 signaling in fission yeast. Current Biology. 2010 Nov 23;20(22):1975-1982. https://doi.org/10.1016/j.cub.2010.10.026
Tatebe, Hisashi ; Morigasaki, Susumu ; Murayama, Shinichi ; Zeng, Cui Tracy ; Shiozaki, Kazuhiro. / Rab-Family GTPase regulates TOR complex 2 signaling in fission yeast. In: Current Biology. 2010 ; Vol. 20, No. 22. pp. 1975-1982.
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