SEACing the GAP that nEGOCiates TORC1 activation: evolutionary conservation of Rag GTPase regulation

Cell Cycle. 2013 Sep 15;12(18):2948-52. doi: 10.4161/cc.26000. Epub 2013 Aug 13.

Abstract

The target of rapamycin complex 1 (TORC1) regulates eukaryotic cell growth in response to a variety of input signals. In S. cerevisiae, amino acids activate TORC1 through the Rag guanosine triphosphatase (GTPase) heterodimer composed of Gtr1 and Gtr2 found together with Ego1 and Ego3 in the EGO complex (EGOC). The GTPase activity of Gtr1 is regulated by the SEA complex (SEAC). Specifically, SEACIT, a SEAC subcomplex containing Iml1, Npr2, and Npr3 functions as a GTPase activator (GAP) for Gtr1 to decrease the activity of TORC1 and, consequently, growth, after amino acid deprivation. Here, we present genetic epistasis data, which show that SEACAT, the other SEAC subcomplex, containing Seh1, Sea2-4, and Sec13, antagonizes the GAP function of SEACIT. Orthologs of EGOC (Ragulator), SEACIT (GATOR1), and SEACAT (GATOR2) are present in higher eukaryotes, highlighting the remarkable conservation, from yeast to man, of Rag GTPase and TORC1 regulation.

Keywords: EGO complex; GATOR1; GATOR2; Iml1-Npr2-Npr3 Rag GTPase GAP complex; Rag GTPases; SEA complex; Sec13; Seh1; TOR complex 1; amino acid signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GTP Phosphohydrolases / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins / metabolism
  • Multiprotein Complexes / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • GTR2 protein, S cerevisiae
  • Gtr1 protein, S cerevisiae
  • Iml1 protein, S cerevisiae
  • Intracellular Signaling Peptides and Proteins
  • MEH1 protein, S cerevisiae
  • Multiprotein Complexes
  • NPR2 protein, S cerevisiae
  • NPR3 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • SEC13 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Seh1 protein, S cerevisiae
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • GTP Phosphohydrolases
  • Monomeric GTP-Binding Proteins