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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
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Rab5 proteins regulate activation and localization of target of rapamycin complex 1

Dave Bridges1, Kaleigh Fisher, Sergey N Zolov

  • 1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.

The Journal of Biological Chemistry
|May 2, 2012
PubMed

Insights

The small GTPase Rab5 and its yeast homolog Vps21 are crucial for the localization and activation of mechanistic target of rapamycin (mTOR) complex 1. Their role in phosphoinositide synthesis is essential for mTORC1 function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mechanistic target of rapamycin (mTOR) complex 1 (TORC1) is a central regulator of cell growth and metabolism.
  • TORC1 activity is tightly controlled by various signaling pathways, including those involving small GTPases and cellular localization.

Purpose of the Study:

  • To investigate the role of the small GTPase Rab5 in the localization and activation of TORC1.
  • To determine if this role is conserved across different species, specifically in yeast and mammalian cells.

Main Methods:

  • Utilized Rab5 mutants in mammalian cells to assess TORC1 activation and localization.
  • Disrupted the yeast homolog of Rab5, Vps21, to evaluate its impact on TORC1 function.
  • Examined the regulation of phosphoinositide 3-phosphate (PI(3)P) synthesis by Rab5 and Vps21.

Main Results:

  • Rab5 mutants impaired TORC1 activation and localization in mammalian cells.
  • Disruption of Vps21 in yeast led to reduced TORC1 function.
  • Rab5 and Vps21-mediated regulation of PI(3)P synthesis was found to be critical for TORC1 function in both cell types.

Conclusions:

  • The small GTPase Rab5 and its yeast homolog Vps21 play a conserved role in TORC1 regulation.
  • Proper localization and activation of TORC1 depend on Rab5/Vps21 function and associated phosphoinositide synthesis.

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