RRC ID 49528
著者 Matsui T, Fukuda M.
タイトル Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.
ジャーナル EMBO Rep
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.
巻・号 14(5)
ページ 450-7
公開日 2013-5-1
DOI 10.1038/embor.2013.32
PII embor201332
PMID 23478338
PMC PMC3642374
MeSH 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*
IF 7.497
引用数 47
リソース情報
遺伝子材料 pMRX-puro-HA-mouse PAT4 (RDB15392).