Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4

EMBO Rep. 2013 May;14(5):450-7. doi: 10.1038/embor.2013.32. Epub 2013 Mar 12.


Autophagy is an evolutionarily conserved catabolic mechanism that targets intracellular molecules and damaged organelles to lysosomes. Autophagy is achieved by a series of membrane trafficking events, but their regulatory mechanisms are poorly understood. Here, we report small GTPase Rab12 as a new type of autophagic regulator that controls the degradation of an amino-acid transporter. Knockdown of Rab12 results in inhibition of autophagy and in increased activity of mTORC1 (mammalian/mechanistic target of rapamycin complex 1), an upstream regulator of autophagy. We also found that Rab12 promotes constitutive degradation of PAT4 (proton-coupled amino-acid transporter 4), whose accumulation in Rab12-knockdown cells modulates mTORC1 activity and autophagy. Our findings reveal a new mechanism of regulation of mTORC1 signalling and autophagy, that is, quality control of PAT4 by Rab12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / metabolism*
  • Animals
  • Autophagy*
  • Cells, Cultured
  • Gene Knockdown Techniques
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes / metabolism*
  • Proteolysis*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • rab GTP-Binding Proteins / physiology*


  • Amino Acid Transport Systems
  • Multiprotein Complexes
  • PAT4 protein, mouse
  • RNA, Small Interfering
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • rab12 protein, mouse
  • rab GTP-Binding Proteins