The Journal of biological chemistrySep 13, 2025

TOR signaling controls receptor levels on the cell surface and reduces yeast mating activity

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

TOR complexes regulate GPCR signaling by controlling receptor endocytosis in yeast.

TORC1 inhibition promotes the internalization of the mating GPCR, Ste2.
The process involves TORC2, the kinase Ypk1, and the α-arrestins Rod1 and Rog3.
Atg8 is utilized during mating to transport the active receptor to the vacuole, inhibiting the mating pathway.
TOR influences both ligand-dependent and ligand-independent signaling of the yeast mating GPCR.
TORC2 activity is essential for endocytosis of Ste2 triggered by rapamycin and pheromones.
The findings suggest that the TOR regulation of GPCRs may be a conserved mechanism across species.

Simplified

Target of rapamycin (TOR) complexes and G protein-coupled receptors (GPCRs) are crucial signaling hubs that coordinate adaptive responses to environmental inputs. While GPCR-mediated regulation of TOR has been extensively studied, little is known about TOR-mediated regulation of GPCRs. Here, we establish TOR as a regulator of GPCR signaling via its control of receptor endocytosis in the yeast mating system. By pairing fluorescence microscopy with yeast genetic approaches, we identify the machinery that bridges TOR nutrient sensing to internalization of the mating GPCR, Ste2. We found that TORC1 inhibition drives internalization of Ste2 through TORC2, the kinase Ypk1, and the α-arrestins Rod1 and Rog3. Furthermore, we find that Atg8, a central player in autophagy, is employed during mating to deliver active receptor to the vacuole (lysosome), suppressing the mating pathway. These results demonstrate that TOR regulates the localization and signaling of the yeast mating GPCR in both ligand-dependent and ligand-independent contexts. We found that TORC2 activity is required for both rapamycin-driven and pheromone-driven endocytosis of Ste2. These pathways are highly conserved suggesting that TOR regulation of GPCRs may be a broadly conserved mechanism for integrating competing signals involving metabolic state and external communications.

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Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

PubMed

TOR signaling controls receptor levels on the cell surface and reduces yeast mating activity

Abstract

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Competing interests

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Abstract

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