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PMID: 22696681 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1.

Molecular biology of the cell ·Vol. 23 ·No. 15 ·2012-08-00 ·Pages 2955-62

Bridges D, Ma JT, Park S, Inoki K, Weisman LS, Saltiel AR

Abstract

The kinase complex mechanistic target of rapamycin 1 (mTORC1) plays an important role in controlling growth and metabolism. We report here that the stepwise formation of phosphatidylinositol 3-phosphate (PI(3)P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P(2)) regulates the cell type-specific activation and localization of mTORC1. PI(3)P formation depends on the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α, as well as the class III PI3K Vps34, while PI(3,5)P(2) requires the phosphatidylinositol-3-phosphate-5-kinase PIKFYVE. In this paper, we show that PIKFYVE and PI3K-C2α are necessary for activation of mTORC1 and its translocation to the plasma membrane in 3T3-L1 adipocytes. Furthermore, the mTORC1 component Raptor directly interacts with PI(3,5)P(2). Together these results suggest that PI(3,5)P(2) is an essential mTORC1 regulator that defines the localization of the complex.

MeSH Terms
3T3-L1 Cells Adaptor Proteins, Signal Transducing/metabolism Adipocytes/cytology,metabolism Animals Cell Membrane/metabolism Class III Phosphatidylinositol 3-Kinases/metabolism HEK293 Cells Humans Insulin/metabolism Lipid Metabolism Mechanistic Target of Rapamycin Complex 1 Mice Multiprotein Complexes Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositol Phosphates/metabolism Proteins/metabolism Regulatory-Associated Protein of mTOR Signal Transduction TOR Serine-Threonine Kinases
Chemicals
Adaptor Proteins, Signal Transducing Insulin Multiprotein Complexes Phosphatidylinositol Phosphates Proteins RPTOR protein, human Regulatory-Associated Protein of mTOR phosphatidylinositol 3,5-diphosphate phosphatidylinositol 3-phosphate Class III Phosphatidylinositol 3-Kinases PIK3C2A protein, human PIKFYVE protein, human Mechanistic Target of Rapamycin Complex 1 TOR Serine-Threonine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bridges Dave
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Ma Jing-Tyan
Park Sujin
Inoki Ken
Weisman Lois S
Saltiel Alan R
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.E11-12-1034
Published
2012-08-00
Epub
2012-00-13
Pages
2955-62
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC3408421
Subset
IM
Grants
NIDDK NIH HHS · R01 DK083491 · United States
NIGMS NIH HHS · 1R01GM5040316 · United States
NIDDK NIH HHS · R01 DK061618 · United States
NIDDK NIH HHS · 5R01DK061618 · United States
NIDDK NIH HHS · P30 DK020572 · United States
NINDS NIH HHS · R01 NS064015 · United States
NIDDK NIH HHS · DK060597 · United States
NIDDK NIH HHS · R01 DK060597 · United States
NIDDK NIH HHS · 1R01DK083491 · United States
External Links
PubMed source DOI: 10.1091/mbc.E11-12-1034 PMC Full Text View journal details
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