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Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

Robbie Loewith1, Estela Jacinto, Stephan Wullschleger

  • 1Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.

Molecular Cell
|November 1, 2002
PubMed

Insights

The target of rapamycin (TOR) proteins form two distinct complexes, TORC1 and TORC2. These complexes mediate different cellular functions, explaining the diverse and specific effects of rapamycin on TOR signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Target of rapamycin (TOR) proteins regulate essential cellular processes.
  • TOR1 and TOR2 in Saccharomyces cerevisiae exhibit redundant growth regulation sensitive to rapamycin.
  • TOR2 uniquely controls actin cytoskeleton polarization independently of rapamycin.

Purpose of the Study:

  • To elucidate the distinct functional roles of TOR complexes.
  • To differentiate the rapamycin-sensitive and insensitive pathways mediated by TOR proteins.
  • To characterize the composition of TOR complexes and their relationship to rapamycin sensitivity.

Main Methods:

  • Biochemical analysis to identify components of TOR complexes.
  • Genetic disruption of TOR complexes to assess functional consequences.
  • Investigation of FKBP-rapamycin binding to distinct TOR complexes.

Main Results:

  • Two functionally distinct TOR complexes were identified: TORC1 and TORC2.
  • TORC1, containing TOR1 or TOR2, is sensitive to FKBP-rapamycin and mediates shared pathways.
  • TORC2, containing TOR2 and specific components, is insensitive to FKBP-rapamycin and regulates actin polarization.

Conclusions:

  • Distinct TOR complexes (TORC1 and TORC2) explain the specificity of TOR signaling.
  • TORC1 mediates rapamycin-sensitive growth regulation, while TORC2 mediates rapamycin-insensitive actin polarization.
  • These TOR complexes are conserved from yeast to humans, indicating fundamental biological roles.

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