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

5 Scopus citations


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
Issue number20
StatePublished - May 17 2022


  • SNAT7
  • mTOR
  • macropinocytosis

ASJC Scopus subject areas

  • General


Dive into the research topics of 'SNAT7 regulates mTORC1 via macropinocytosis'. Together they form a unique fingerprint.

Cite this