# Dissection of the TORC1 Signaling Network in Yeast

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $343,948

## Abstract

SUMMARY/ABSTRACT
The Target of Rapamycin kinase Complex I (TORC1) is a key regulator of cell growth and metabolism in
eukaryotes. Work carried out over the last 15 years has shed light on the mechanisms underlying hormone
and amino acid signaling to TORC1, but it is still unclear how other key signals, such as glucose starvation, are
transmitted to this highly conserved complex. In the last grant period, we examined TORC1 signaling in
budding yeast and found that glucose starvation leads to rapid inactivation of the TORC1 pathway. Then, in a
slower reaction (τ=10min), TORC1 falls apart and the key regulatory component Kog1/Raptor moves into a
single body on the edge of the vacuole/lysosome. The latter event is driven (in part) by AMPK/Snf1 dependent
phosphorylation of Kog1 at Ser 491/494, and two nearby prion-like motifs. Kog1-bodies then serve to increase
the threshold of TORC1 activation and ensure that cells remain committed to a quiescent state in suboptimal
conditions. More recently, we found that the EGO complex (EGOC; Rag/Ragulator in humans)—known to
activate TORC1 in the presence of amino acids—also moves into Kog1-bodies. Following up on these data
we will now determine: (A) How glucose starvation triggers inhibition of the TORC1 pathway; (B) What proteins
are in Kog1/EGOC-bodies; (C) What drives assembly of the Kog1/EGOC-bodies; and, (D) What role
Kog1/EGOC-bodies play in cell signaling. To do this we will: (1) Dissect the structure and function of Kog1-
bodies. In preliminary experiments we have shown that the Kog1/EGOC bodies remain intact on purified
vacuoles. Taking advantage of this, we will now map the composition of the Kog1/EGOC-body and its
assembly pathway. Then, using mutants that have defects in Kog/EGOC-body assembly (including some we
have already isolated), we will test our prediction that Kog1-bodies play a role in (a) bet hedging, (b) noise
dampening, and (c) the coordination of stress and starvation responses. We will also: (2) Identify the proteins
that regulate the TORC1 pathway and Kog1/EGOC-body formation, and dissect their mechanism of action. In
this aim, we will test the predication that glucose starvation and AMPK/Snf1, trigger changes in EGOC to
inactivate TORC1 and drive the formation of Kog1/EGOC–bodies. To do this we will map the circuit that
regulates TORC1 signaling and Kog1-body formation, and then study the function of key regulators (including
two we recently identified) in detail. Our proposal is innovative in that we study new and unexplored aspects of
TORC1 signaling using state-of-the-art systems, genomic, and biochemical approaches. The proposed
research is significant in that it promises to shed light on the mechanisms underlying cell growth control in
humans and/or lower eukaryotes—with implications for (a) understanding TORC1 related diseases such as
cancer, diabetes and obesity, and (b) developing drugs that selectively block the growth of pathogenic fungi.
In addition, our work promises to s...

## Key facts

- **NIH application ID:** 9873039
- **Project number:** 5R01GM097329-09
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Andrew Paul Capaldi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,948
- **Award type:** 5
- **Project period:** 2011-09-30 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873039

## Citation

> US National Institutes of Health, RePORTER application 9873039, Dissection of the TORC1 Signaling Network in Yeast (5R01GM097329-09). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/9873039. Licensed CC0.

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