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

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54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)450-457
Number of pages8
JournalEMBO Reports
Volume14
Issue number5
DOIs
Publication statusPublished - 2013 May

Keywords

  • Rab12
  • amino-acid transporter
  • autophagy
  • mTORC1
  • recycling endosome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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