SNAT7 regulates mTORC1 via macropinocytosis

Delong Meng, Qianmei Yang, Mi Hyeon Jeong, Adna Curukovic, Shweta Tiwary, Chase H. Melick, Tshering D. Lama-Sherpa, Huanyu Wang, Mariela Huerta-Rosario, Greg Urquhart, Lauren G. Zacharias, Cheryl Lewis, Ralph J. DeBerardinis, Jenna L. Jewell

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Mammalian target of rapamycin complex 1 (mTORC1) senses amino acids to control cell growth, metabolism, and autophagy. Some amino acids signal to mTORC1 through the Rag GTPase, whereas glutamine and asparagine activate mTORC1 through a Rag GTPase-independent pathway. Here, we show that the lysosomal glutamine and asparagine transporter SNAT7 activates mTORC1 after extracellular protein, such as albumin, is macropinocytosed. The N terminus of SNAT7 forms nutrient-sensitive interaction with mTORC1 and regulates mTORC1 activation independently of the Rag GTPases. Depletion of SNAT7 inhibits albumin-induced mTORC1 lysosomal localization and subsequent activation. Moreover, SNAT7 is essential to sustain KRAS-driven pancreatic cancer cell growth through mTORC1. Thus, SNAT7 links glutamine and asparagine signaling from extracellular protein to mTORC1 independently of the Rag GTPases and is required for macropinocytosis-mediated mTORC1 activation and pancreatic cancer cell growth.

Original languageEnglish (US)
Article numbere2123261119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number20
DOIs
StatePublished - May 17 2022

Keywords

  • SNAT7
  • mTOR
  • macropinocytosis

ASJC Scopus subject areas

  • General

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