Rheb localized on the Golgi membrane activates lysosome-localized mTORC1 at the Golgi-lysosome contact site

J Cell Sci. 2018 Jan 29;131(3):jcs208017. doi: 10.1242/jcs.208017.

Abstract

In response to amino acid supply, mTORC1, a master regulator of cell growth, is recruited to the lysosome and activated by the small GTPase Rheb. However, the intracellular localization of Rheb is controversial. In this study, we showed that a significant portion of Rheb is localized on the Golgi but not on the lysosome. GFP-Rheb could activate mTORC1, even when forced to exclusively localize to the Golgi. Likewise, artificial recruitment of mTORC1 to the Golgi allowed its activation. Accordingly, the Golgi was in contact with the lysosome at an newly discovered area of the cell that we term the Golgi-lysosome contact site (GLCS). The number of GLCSs increased in response to amino acid supply, whereas GLCS perturbation suppressed mTORC1 activation. These results suggest that inter-organelle communication between the Golgi and lysosome is important for mTORC1 regulation and the Golgi-localized Rheb may activate mTORC1 at GLCSs.

Keywords: Golgi; Lysosome; Organelle contact site; Rheb; mTORC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / metabolism*
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism*
  • Lysosomes / drug effects
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Protein Transport / drug effects
  • Ras Homolog Enriched in Brain Protein / metabolism*

Substances

  • Amino Acids
  • Ras Homolog Enriched in Brain Protein
  • Green Fluorescent Proteins
  • Mechanistic Target of Rapamycin Complex 1