Aster-C coordinates with COP I vesicles to regulate lysosomal trafficking and activation of mTORC1

Jun Zhang, John Paul Andersen, Haoran Sun, Xuyun Liu, Nahum Sonenberg, Jia Nie, Yuguang Shi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Nutrient sensing by the mTOR complex 1 (mTORC1) requires its translocation to the lysosomal membrane. Upon amino acids removal, mTORC1 becomes cytosolic and inactive, yet its precise subcellular localization and the mechanism of inhibition remain elusive. Here, we identified Aster-C as a negative regulator of mTORC1 signaling. Aster-C earmarked a special rough ER subdomain where it sequestered mTOR together with the GATOR2 complex to prevent mTORC1 activation during nutrient starvation. Amino acids stimulated rapid disassociation of mTORC1 from Aster-C concurrently with assembly of COP I vesicles which escorted mTORC1 to the lysosomal membrane. Consequently, ablation of Aster-C led to spontaneous activation of mTORC1 and dissociation of TSC2 from lysosomes, whereas inhibition of COP I vesicle biogenesis or actin dynamics prevented mTORC1 activation. Together, these findings identified Aster-C as a missing link between lysosomal trafficking and mTORC1 activation by revealing an unexpected role of COP I vesicles in mTORC1 signaling.

Original languageEnglish (US)
Article numbere49898
JournalEMBO Reports
Volume21
Issue number9
DOIs
StatePublished - Sep 3 2020

Keywords

  • ARF1
  • COP I
  • GRAMD1C
  • lysosomes
  • mTORC1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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