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Updated: Sep 23, 2025
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Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes
Published on: August 24, 2021
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SNAT7 regulates mTORC1 via macropinocytosis
Delong Meng1,2,3, Qianmei Yang1,2,3, Mi-Hyeon Jeong1,2,3
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Summary
The SNAT7 transporter activates the mTORC1 pathway by sensing extracellular proteins like albumin. This process, crucial for cell growth and in KRAS-driven pancreatic cancer, bypasses the Rag GTPase pathway.
Area of Science:
- Cellular Biology
- Molecular Biology
- Cancer Research
Background:
- Mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth, metabolism, and autophagy in response to amino acid availability.
- Amino acid signaling to mTORC1 involves Rag GTPases, but glutamine and asparagine utilize a Rag GTPase-independent pathway.
Purpose of the Study:
- To investigate the role of the lysosomal transporter SNAT7 in mTORC1 activation.
- To elucidate the mechanism by which SNAT7 links extracellular protein sensing to mTORC1 signaling independently of Rag GTPases.
- To determine the significance of SNAT7 in KRAS-driven pancreatic cancer cell growth.
Main Methods:
- Investigated SNAT7's interaction with mTORC1 using nutrient-sensitive assays.
- Utilized SNAT7 depletion to assess its role in albumin-induced mTORC1 activation and lysosomal localization.
- Examined the requirement of SNAT7 for KRAS-driven pancreatic cancer cell proliferation.
Main Results:
- SNAT7 activates mTORC1 following macropinocytosis of extracellular proteins like albumin, independent of Rag GTPases.
- The N terminus of SNAT7 mediates nutrient-sensitive interactions with mTORC1.
- SNAT7 depletion abrogates albumin-induced mTORC1 lysosomal localization and activation, and impairs KRAS-driven pancreatic cancer growth.
Conclusions:
- SNAT7 acts as a critical link between extracellular protein-derived glutamine and asparagine and mTORC1 activation via a Rag GTPase-independent mechanism.
- SNAT7 is essential for macropinocytosis-mediated mTORC1 activation.
- SNAT7 plays a vital role in sustaining pancreatic cancer cell growth.
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