title: TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor.
abstract: The TORC1 kinase signaling complex is a key determinant of cell growth that senses nutritional status and responds by coordinating diverse cellular processes including transcription, translation, and autophagy. Here, we demonstrate that TORC1 modulates the composition of plasma membrane (PM) proteins by regulating ubiquitin-mediated endocytosis. The mechanism involves the Npr1 kinase, a negative regulator of endocytosis that is itself negatively regulated by TORC1. We show that Npr1 inhibits the activity of Art1, an arrestin-like adaptor protein that promotes endocytosis by targeting the Rsp5 ubiquitin ligase to specific PM cargoes. Npr1 antagonizes Art1-mediated endocytosis via N-terminal phosphorylation, a modification that prevents Art1 association with the PM. Thus, our study adds ubiquitin ligase targeting and control of endocytosis to the known effector mechanisms of TORC1, underscoring how TORC1 coordinates ubiquitin-mediated endocytosis with protein synthesis and autophagy in order to regulate cell growth.
authors: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
authors: Jason A
authors: JA
authors: MacGurn
authors: Pi-Chiang
authors: PC
authors: Hsu
authors: Marcus B
authors: MB
authors: Smolka
authors: Scott D
authors: SD
authors: Emr
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004705:Endocytosis; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D004268:DNA-Binding Proteins; C062214:SWI4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; C066958:NPR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases