Endoplasmic Reticulum and Golgi Localization Sequences for Mammalian Target of Rapamycin
- 1 March 2007
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 18 (3), 1073-1082
- https://doi.org/10.1091/mbc.e06-05-0406
Abstract
Mammalian target of rapamycin (mTOR) forms two complexes, mTORC1 and mTORC2, that play central roles in cell growth and functions. Only mTORC1 is directly inhibited by the immunosuppressive drug rapamycin. Despite recent progress in identifying new components and functions of the mTOR pathway, relatively little is known about the spatial arrangement of mTOR signaling and the underlying mechanisms. In a previous study, we showed that a large proportion of mTOR is localized to the endoplasmic reticulum (ER) and Golgi in many common cell lines. Here, we report the identification of an internal mTOR sequence that contains two HEAT (HT) repeats, HT18 and HT19, and two intervening interunit spacers (IUSs), IUS17 and IUS18, which is sufficient to target enhanced green fluorescent protein to the Golgi. Surprisingly, deletion of IUS17 from this Golgi localization sequence (GLS) converts it to an ER localization sequence (ELS). Deletion of HT19, a common element of both GLS and ELS from the full-length mTOR, causes delocalization of mTOR and inhibits the ability of mTOR to promote S6 phosphorylation. Moreover, overexpression of GLS and ELS inhibits both mTOR complexes. Together, our results reveal unusual ER- and Golgi-targeting sequences and suggest that anchoring to these organelles is important for the functions of mTOR complexes.Keywords
This publication has 60 references indexed in Scilit:
- Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activityGenes & Development, 2006
- Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR ComplexScience, 2005
- Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitiveNature, 2004
- Tuberin is a component of lipid rafts and mediates caveolin-1 localization: role of TSC2 in post-Golgi transportExperimental Cell Research, 2004
- Tor Kinases Are in Distinct Membrane-associated Protein Complexes inSaccharomyces cerevisiaeMolecular Biology of the Cell, 2003
- Cholesterol Addition to ER Membranes Alters Conformation of SCAP, the SREBP Escort Protein that Regulates Cholesterol MetabolismMolecular Cell, 2002
- mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth MachineryCell, 2002
- Sterol-Regulated Release of SREBP-2 from Cell Membranes Requires Two Sequential Cleavages, One Within a Transmembrane SegmentCell, 1996
- PIK-Related Kinases: DNA Repair, Recombination, and Cell Cycle CheckpointsScience, 1995
- HEAT repeats in the Huntington's disease proteinNature Genetics, 1995