# Regulation by mTORC1 of the lysosomal efflux of essential amino acids

> **NIH NIH F30** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $38,321

## Abstract

Project Summary/Abstract
 The mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase which
coordinates cell growth and metabolism by balancing anabolic and catabolic processes in response to
nutrients, growth factor signaling, and energy levels 1,2. Deregulated signaling in this pathway has been
implicated in many human diseases including neurodegeneration, diabetes, and cancer3. As such, the
mechanisms involved in mTORC1 activation and the biological processes under the control of mTORC1 are of
significant interest.
 Lysosomes play a crucial role in the signal transduction of the nutrient sensing branch of the mTORC1
pathway9. While developing a novel tool for the rapid isolation of pure lysosomes, we made the surprising
discovery that mTORC1 regulates the lysosomal concentration of a distinct set of non-polar, mostly essential
amino acids. Using the same method, we noticed that loss of SLC38A9, a largely unstudied amino acid
transporter that senses lysosomal arginine, results in the accumulation of the same set of non-polar, mostly
essential amino acids. Despite this knowledge, the mechanism by which mTORC1 regulates the lysosomal
abundance of essential amino acids through SLC38A9 is not known. Elucidation of this mechanism will give
key insights into how mammalian cells respond to nutrient availability and may also provide novel therapeutic
targets for the treatment of tumors.
 Preliminary evidence suggests the Rag-Ragulator complex, which interacts with SLC38A9 and conveys
the availability of nutrients to mTORC1, is necessary for mTORC1 to regulate the efflux of essential amino
acids from lysosomes. To characterize the molecular mechanism by which mTORC1 regulates SLC38A9
transport function, we propose the following aims:
.
 1. Determine the role of mTORC1 in controlling the interaction between SLC38A9 and Rag-
Ragulator.
2. Understand the role of Rag-Ragulator phosphorylation on the regulation of the transport
 function of SLC38A9.
3. Identification of lysosomal proteins that regulate SLC38A9.

## Key facts

- **NIH application ID:** 10076804
- **Project number:** 5F30CA236179-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Jibril Kedir
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,321
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076804

## Citation

> US National Institutes of Health, RePORTER application 10076804, Regulation by mTORC1 of the lysosomal efflux of essential amino acids (5F30CA236179-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10076804. Licensed CC0.

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