A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans

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 lip...

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Main Authors: Huanhu Zhu, Huali Shen, Aileen K Sewell, Marina Kniazeva, Min Han
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2013-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/00429
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spelling doaj-5e45176b82164dc6af1fc7024f2c808c2021-05-04T22:27:02ZengeLife Sciences Publications LtdeLife2050-084X2013-05-01210.7554/eLife.00429A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegansHuanhu Zhu0Huali Shen1Aileen K Sewell2Marina Kniazeva3Min Han4Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, United States; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United StatesHoward Hughes Medical Institute, University of Colorado, Boulder, Boulder, United States; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United States; Department of Chemistry and Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaHoward Hughes Medical Institute, University of Colorado, Boulder, Boulder, United States; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United StatesHoward Hughes Medical Institute, University of Colorado, Boulder, Boulder, United States; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United StatesHoward Hughes Medical Institute, University of Colorado, Boulder, Boulder, United States; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United StatesRegulation 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.https://elifesciences.org/articles/00429branched-chain fatty acidgrowth arrestnutrient sensingNPRLglucosylceramidetarget of rapamycin
collection DOAJ
language English
format Article
sources DOAJ
author Huanhu Zhu
Huali Shen
Aileen K Sewell
Marina Kniazeva
Min Han
spellingShingle Huanhu Zhu
Huali Shen
Aileen K Sewell
Marina Kniazeva
Min Han
A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans
eLife
branched-chain fatty acid
growth arrest
nutrient sensing
NPRL
glucosylceramide
target of rapamycin
author_facet Huanhu Zhu
Huali Shen
Aileen K Sewell
Marina Kniazeva
Min Han
author_sort Huanhu Zhu
title A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans
title_short A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans
title_full A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans
title_fullStr A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans
title_full_unstemmed A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans
title_sort novel sphingolipid-torc1 pathway critically promotes postembryonic development in caenorhabditis elegans
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2013-05-01
description 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.
topic branched-chain fatty acid
growth arrest
nutrient sensing
NPRL
glucosylceramide
target of rapamycin
url https://elifesciences.org/articles/00429
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