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The Vam6 GEF controls TORC1 by activating the EGO complex

Matteo Binda1, Marie-Pierre Péli-Gulli, Grégory Bonfils

  • 1Department of Medicine, University of Fribourg, Switzerland.

Molecular Cell
|September 15, 2009
PubMed

Insights

Yeast Gtr1, part of the EGO complex, activates the nutrient-sensing TORC1 pathway. Its nucleotide status, controlled by Vam6, dictates TORC1 activity, impacting cell growth regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The target of rapamycin complex 1 (TORC1) is a crucial regulator of eukaryotic cell growth.
  • TORC1 activity is influenced by hormones and nutrients, and its dysregulation is linked to cancer.
  • The EGO complex (EGOC) is involved in TORC1 regulation.

Purpose of the Study:

  • To investigate the role of the yeast Rag GTPase homolog Gtr1 in TORC1 activation.
  • To elucidate the regulatory mechanism of Gtr1 by the guanine nucleotide exchange factor Vam6.

Main Methods:

  • Yeast genetics and molecular biology techniques.
  • Analysis of protein-protein interactions between Gtr1 and TORC1.
  • Assessment of TORC1 activity under different nutrient conditions and Gtr1 nucleotide-binding states.

Main Results:

  • Gtr1 interacts with and activates TORC1 in an amino-acid-dependent manner.
  • Constitutively active Gtr1 (Gtr1(GTP)) enhances TORC1 activity and confers resistance to leucine deprivation.
  • GDP-bound Gtr1 (Gtr1(GDP)) leads to low TORC1 activity.
  • Vam6 regulates the nucleotide-binding status of Gtr1, thereby controlling TORC1 function.

Conclusions:

  • Gtr1 is a key component linking the EGO complex to TORC1 signaling.
  • Vam6 acts as a guanine nucleotide exchange factor for Gtr1, modulating TORC1 activity.
  • This pathway is essential for nutrient sensing and cell growth regulation in yeast.

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