Open AccessThe Rheb-TORC1 signaling axis functions as a developmental checkpoint
Author(s) -
Thien Duong,
Neal R. Rasmussen,
Elliot Ballato,
Francisca Sefakor Mote,
David J. Reiner
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.181727
Subject(s) - biology , rheb , microbiology and biotechnology , tor signaling , signal transduction , cancer research , pi3k/akt/mtor pathway , mtorc1
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 C. elegans RHEB-1 and DAF-15/Raptor are expressed ubiquitously and localize to lysosomes. Disruption of LET-363/TOR and DAF-15/Raptor are required for development past 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 at each stage the decision of the animal to progress through development.