Reference - Detail
RRC ID | 59484 |
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Author | Duong T, Rasmussen NR, Ballato E, Mote FS, Reiner DJ. |
Title | The Rheb-TORC1 signaling axis functions as a developmental checkpoint. |
Journal | Development |
Abstract |
In many eukaryotes, the small GTPase Rheb functions as a switch to toggle activity of TOR complex 1 (TORC1) between anabolism and catabolism, thus controlling lifespan, development and autophagy. Our CRISPR-generated, fluorescently tagged endogenous Caenorhabditis elegans RHEB-1 and DAF-15/Raptor are expressed ubiquitously and localize to lysosomes. LET-363/TOR and DAF-15/Raptor are required for development beyond the third larval stage (L3). We observed that deletion of RHEB-1 similarly conferred L3 arrest. Unexpectedly, robust RNAi-mediated depletion of TORC1 components caused arrest at stages prior to L3. Accordingly, conditional depletion of endogenous DAF-15/Raptor in the soma revealed that TORC1 is required at each stage of the life cycle to progress to the next stage. Reversal of DAF-15 depletion permits arrested animals to recover to continue development. Our results are consistent with TORC1 functioning as a developmental checkpoint that governs the decision of the animal to progress through development. |
Volume | 147(5) |
Published | 2020-3-2 |
DOI | 10.1242/dev.181727 |
PII | dev.181727 |
PMID | 32041790 |
PMC | PMC7063671 |
MeSH | Animals Animals, Genetically Modified Autophagy / physiology CRISPR-Cas Systems / genetics Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Life Cycle Stages / genetics Longevity / physiology Mechanistic Target of Rapamycin Complex 1 / genetics Mechanistic Target of Rapamycin Complex 1 / metabolism* Phosphotransferases (Alcohol Group Acceptor) / genetics* RNA Interference RNA, Small Interfering / genetics Ras Homolog Enriched in Brain Protein / genetics Ras Homolog Enriched in Brain Protein / metabolism* Signal Transduction |
IF | 5.763 |
Times Cited | 0 |
Resource | |
C.elegans | tm4931 tm4642 |