Related Experiment Video
Updated: May 29, 2026
Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
A shift of the TOR adaptor from Rictor towards Raptor by semaphorin in C. elegans
Akira Nukazuka1, Shusaku Tamaki, Kunihiro Matsumoto
1Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-8602, Japan.
Abstract:
The target of rapamycin (TOR), a central regulator for cell growth and metabolism, resides in the two functionally distinct complexes TORC1 and TORC2, which are defined by their adaptors Raptor and Rictor, respectively. How the formation of the two TORCs is orchestrated remains unclear. Here we show the control of TOR partnering by semaphorin-plexin signalling in Caenorhabditis elegans. In semaphorin and plexin mutants, TOR-Raptor association decreases whereas TOR-Rictor association increases, concomitantly with TORC1 down- and TORC2 up-regulation. Epidermal defects in the mutants are suppressed by inhibiting TORC2 or reinforcing TORC1 signalling. Conversely, inhibition of TORC1 signalling phenocopies the mutants. Thus, our results indicate that TORC formation is a singularly important step in semaphorin signalling that culminates in diverse outcomes including TORC1-promoted messenger RNA translation and TORC2-regulated cytoskeletal remodelling.
Insights
Semaphorin-plexin signaling controls the formation of distinct mTORC1 and mTORC2 complexes in C. elegans. This regulation is crucial for cell growth, metabolism, and developmental processes like cytoskeletal remodeling and mRNA translation.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- The target of rapamycin (TOR) pathway regulates cell growth and metabolism.
- TOR exists in two complexes, TORC1 and TORC2, with distinct functions.
- The mechanisms orchestrating TORC1 and TORC2 formation are not fully understood.
Purpose of the Study:
- To investigate the role of semaphorin-plexin signaling in regulating TORC1 and TORC2 complex formation.
- To elucidate how TORC assembly influences downstream cellular processes.
Main Methods:
- Utilized Caenorhabditis elegans as a model organism.
- Generated and analyzed semaphorin and plexin mutants.
- Assessed TOR-Raptor and TOR-Rictor associations.
- Examined TORC1 and TORC2 activity levels.
- Investigated epidermal defects and utilized genetic manipulations to modulate TORC activity.
Main Results:
- Semaphorin and plexin mutations altered TOR complex composition, decreasing TOR-Raptor and increasing TOR-Rictor association.
- TORC1 activity was downregulated, while TORC2 activity was upregulated in mutants.
- Genetic manipulation of TORC1 and TORC2 signaling could rescue or phenocopy mutant phenotypes, respectively.
- TORC formation is a critical regulatory step in semaphorin signaling.
Conclusions:
- Semaphorin-plexin signaling directly controls the assembly of TORC1 and TORC2.
- Differential TORC formation impacts key cellular functions including mRNA translation and cytoskeletal organization.
- This study reveals a novel link between guidance signaling and nutrient/growth pathways.
