title: A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans.
abstract: Regulation of animal development in response to nutritional cues is an intensely studied problem related to disease and aging. While extensive studies indicated roles of the Target of Rapamycin (TOR) in sensing certain nutrients for controlling growth and metabolism, the roles of fatty acids and lipids in TOR-involved nutrient/food responses are obscure. Caenorhabditis elegans halts postembryonic growth and development shortly after hatching in response to monomethyl branched-chain fatty acid (mmBCFA) deficiency. Here, we report that an mmBCFA-derived sphingolipid, d17iso-glucosylceramide, is a critical metabolite in regulating growth and development. Further analysis indicated that this lipid function is mediated by TORC1 and antagonized by the NPRL-2/3 complex in the intestine. Strikingly, the essential lipid function is bypassed by activating TORC1 or inhibiting NPRL-2/3. Our findings uncover a novel lipid-TORC1 signaling pathway that coordinates nutrient and metabolic status with growth and development, advancing our understanding of the physiological roles of mmBCFAs, ceramides, and TOR. DOI:http://dx.doi.org/10.7554/eLife.00429.001.
authors.affiliation: Howard Hughes Medical Institute, University of Colorado, Boulder , Boulder , United States ; Department of Molecular, Cellular and Developmental Biology , University of Colorado, Boulder , Boulder , United States.
authors.forename: Huanhu
authors.initials: H
authors.lastname: Zhu
authors.forename: Huali
authors.initials: H
authors.lastname: Shen
authors.forename: Aileen K
authors.initials: AK
authors.lastname: Sewell
authors.forename: Marina
authors.initials: M
authors.lastname: Kniazeva
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005963:Glucosylceramides / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000254:growth & development; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009752:Nutritional Status; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D005963:Glucosylceramides; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: C. elegans; NPRL; branched-chain fatty acid; glucosylceramide; growth arrest; nutrient sensing; target of rapamycin