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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2013-05-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/00429 |
id |
doaj-5e45176b82164dc6af1fc7024f2c808c |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT huanhuzhu anovelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT hualishen anovelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT aileenksewell anovelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT marinakniazeva anovelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT minhan anovelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT huanhuzhu novelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT hualishen novelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT aileenksewell novelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT marinakniazeva novelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans AT minhan novelsphingolipidtorc1pathwaycriticallypromotespostembryonicdevelopmentincaenorhabditiselegans |
_version_ |
1721477294704295936 |