2. Academic Validation
  3. SNAT7 regulates mTORC1 via macropinocytosis

SNAT7 regulates mTORC1 via macropinocytosis

  • Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2123261119. doi: 10.1073/pnas.2123261119.
Delong Meng 1 2 3,  Qianmei Yang 1 2 3,  Mi-Hyeon Jeong 1 2 3,  Adna Curukovic 1 2 3,  Shweta Tiwary 1 2 3,  Chase H Melick 1 2 3,  Tshering D Lama-Sherpa 1 2 3,  Huanyu Wang 1 2 3,  Mariela Huerta-Rosario 2,  Greg Urquhart 1 2 3,  Lauren G Zacharias 4,  Cheryl Lewis 2,  Ralph J DeBerardinis 4 5,  Jenna L Jewell 1 2 3
Affiliations

Affiliations

  • 1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
  • 2 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390.
  • 3 Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
  • 4 Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390.
  • 5 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390.
PMID: 35561222 DOI: 10.1073/pnas.2123261119
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.

Keywords

SNAT7; mTOR; macropinocytosis.

Figures