Starvation-Dependent Regulation of Golgi Quality Control Links the TOR Signaling and Vacuolar Protein Sorting Pathways.
Upon amino acid (AA) starvation and TOR inactivation, plasma-membrane-localized permeases rapidly undergo ubiquitination and internalization via the vacuolar protein sorting/multivesicular body (VPS-MVB) pathway and are degraded in the yeast vacuole. We now show that specific Golgi proteins are also directed to the vacuole under these conditions as part of a Golgi quality-control (GQC) process. The degradation of GQC substrates is dependent upon ubiquitination by the defective-for-SREBP-cleavage (DSC) complex, which was identified via genetic screening and includes the Tul1 E3 ligase. Using a model GQC substrate, GFP-tagged Yif1, we show that vacuolar targeting necessitates upregulation of the VPS pathway via proteasome-mediated degradation of the initial endosomal sorting complex required for transport, ESCRT-0, but not downstream ESCRT components. Thus, early cellular responses to starvation include the targeting of specific Golgi proteins for degradation, a phenomenon reminiscent of the inactivation of BTN1, the yeast Batten disease gene ortholog.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Niv
N
Dobzinski
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Silvia G
SG
Chuartzman
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Rachel
R
Kama
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Maya
M
Schuldiner
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: jeffrey.gerst@weizmann.ac.il.
Jeffrey E
JE
Gerst
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism*; D021381:Protein Transport; D011786:Quality Control; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C473803:YIF1 protein, S cerevisiae; C501306:Ubc4 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D058570:TOR Serine-Threonine Kinases