A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23705068.
- Also identified by DOI 10.7554/eLife.00429 and PMC identifier 3660743.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Glucosylceramides
- Intestinal Mucosa
- Multiprotein Complexes
- Signal Transduction
- TOR Serine-Threonine Kinases