title: TORC2 signaling antagonizes SKN-1 to induce C. elegans mesendodermal embryonic development.
abstract: The evolutionarily conserved target of rapamycin (TOR) kinase controls fundamental metabolic processes to support cell and tissue growth. TOR functions within the context of two distinct complexes, TORC1 and TORC2. TORC2, with its specific component Rictor, has been recently implicated in aging and regulation of growth and metabolism. Here, we identify rict-1/Rictor as a regulator of embryonic development in C. elegans. The transcription factor skn-1 establishes development of the mesendoderm in embryos, and is required for cellular homeostasis and longevity in adults. Loss of maternal skn-1 function leads to mis-specification of the mesendodermal precursor and failure to form intestine and pharynx. We found that genetic inactivation of rict-1 suppressed skn-1-associated lethality by restoring mesendodermal specification in skn-1 deficient embryos. Inactivation of other TORC2 but not TORC1 components also partially rescued skn-1 embryonic lethality. The SGK-1 kinase mediated these functions downstream of rict-1/TORC2, as a sgk-1 gain-of-function mutant suppressed the rict-1 mutant phenotype. These data indicate that TORC2 and SGK-1 antagonize SKN-1 during embryonic development.
authors: Department of Medicine, Renal Division, University Hospital Freiburg, D-79106 Freiburg, Germany.
authors: Vanessa
authors: V
authors: Ruf
authors: Christina
authors: C
authors: Holzem
authors: Tobias
authors: T
authors: Peyman
authors: Gerd
authors: G
authors: Walz
authors: T Keith
authors: TK
authors: Blackwell
authors: Elke
authors: E
authors: Neumann-Haefelin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D004625:Embryo, Nonmammalian / Q000166:cytology*; D004707:Endoderm / Q000196:embryology*; D005804:Genes, Lethal; D000076225:Mechanistic Target of Rapamycin Complex 2; D008648:Mesoderm / Q000196:embryology*; D046912:Multiprotein Complexes / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: C. elegans; Development; RICTOR; SGK-1; SKN-1; TOR signaling
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