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Npr2 regulates autophagy via Gtr1‐Gtr2‐dependent target of rapamycin complex 1 signaling (539.11)
Author(s) -
Noda Takeshi,
Kira Shintaro,
ShirahamaNoda Kanae
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.539.11
Subject(s) - autophagy , microbiology and biotechnology , mutant , gtpase , gtp' , cytosol , intracellular , vacuole , bag3 , chemistry , small gtpase , signal transduction , biology , biochemistry , gene , enzyme , apoptosis , cytoplasm
Autophagy is an intracellular degradation process that delivers cytosolic material to lysosomes and vacuoles. To understand the mechanisms that regulate autophagy, we performed a genome‐wide screen using a yeast deletion mutant collection, and identified Npr2 and Npr3. Mutation of Npr2 and Npr3 disrupted autophagy upstream of Target of Rapamycin Complex 1 (TORC1). Additionally, we found that the Npr2‐Npr3 complexes function upstream of Gtr1‐Gtr2, a GTPase complex that is homologous to Rag. A constitutively active GTP‐bound Gtr1 mutant suppressed autophagy by activating TORC1, whereas a constitutively GDP‐bound Gtr1 mutant induced autophagy. The autophagic defects observed in ∆npr2 cells and cells expressing the GTP‐bound Gtr1 mutant were quite comparable, but different from Gtr1‐GDP expressing cell. We hypothesized that the autophagic defect in the ∆npr2 cells resulted from a defect in the switching of the nucleotide‐binding state of Gtr1. Thus, Npr2‐Npr3 appears to regulate GTP hydrolysis in Gtr1, which affects TORC1 activity and autophagy.