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Endoplasmic reticulum and Golgi localization sequences for mammalian target of rapamycin

Xiangyu Liu1, X F Steven Zheng

  • 1Cancer Institute of New Jersey, Department of Pharmacology, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

Molecular Biology of the Cell
|January 12, 2007
PubMed

Insights

New research identifies specific sequences within the mammalian target of rapamycin (mTOR) that direct its localization to the endoplasmic reticulum (ER) and Golgi apparatus, crucial for cell growth and function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The mammalian target of rapamycin (mTOR) pathway regulates cell growth and function through two complexes, mTORC1 and mTORC2.
  • While mTORC1 is inhibited by rapamycin, the spatial organization of mTOR signaling remains poorly understood.
  • Previous work indicated significant mTOR localization to the ER and Golgi.

Purpose of the Study:

  • To identify and characterize specific sequences within mTOR responsible for its localization to the ER and Golgi.
  • To investigate the functional significance of mTOR's organelle localization for its signaling activities.

Main Methods:

  • Utilized enhanced green fluorescent protein (EGFP) tagging to visualize protein localization.
  • Employed deletion mutagenesis to identify critical regions within mTOR, including HEAT repeats (HT) and interunit spacers (IUS).
  • Assessed the impact of altered localization on mTOR complex activity, specifically S6 phosphorylation.

Main Results:

  • An internal mTOR sequence containing HT18, HT19, IUS17, and IUS18 was identified as sufficient for Golgi targeting (Golgi localization sequence, GLS).
  • Deletion of IUS17 from the GLS converted it into an ER localization sequence (ELS).
  • Deletion of HT19 from full-length mTOR resulted in delocalization and impaired S6 phosphorylation, indicating its importance for mTOR function.

Conclusions:

  • Discovered novel ER- and Golgi-targeting sequences within mTOR.
  • Demonstrated that organelle anchoring of mTOR complexes is essential for their cellular functions.
  • Suggests a regulatory mechanism for mTOR signaling through its spatial arrangement within the cell.

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