title: Unsolved mysteries of Rag GTPase signaling in yeast.
abstract: The target of rapamycin complex 1 (TORC1) plays a central role in controlling eukaryotic cell growth by fine-tuning anabolic and catabolic processes to the nutritional status of organisms and individual cells. Amino acids represent essential and primordial signals that modulate TORC1 activity through the conserved Rag family GTPases. These assemble, as part of larger lysosomal/vacuolar membrane-associated complexes, into heterodimeric sub-complexes, which typically comprise two paralogous Rag GTPases of opposite GTP-/GDP-loading status. The TORC1-stimulating/inhibiting states of these heterodimers are controlled by various guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) complexes, which are remarkably conserved in various eukaryotic model systems. Among the latter, the budding yeast Saccharomyces cerevisiae has been instrumental for the elucidation of basic aspects of Rag GTPase regulation and function. Here, we discuss the current state of the respective research, focusing on the major unsolved issues regarding the architecture, regulation, and function of the Rag GTPase containing complexes in yeast. Decoding these mysteries will undoubtedly further shape our understanding of the conserved and divergent principles of nutrient signaling in eukaryotes.
authors.affiliation: a Department of Biology , University of Fribourg , Fribourg , Switzerland.
authors.forename: Riko
authors.initials: R
authors.lastname: Hatakeyama
authors.affiliation: a Department of Biology , University of Fribourg , Fribourg , Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D020558:GTP Phosphohydrolases
keywords: EGO complex (EGOC); Lst4-Lst7; Rag GTPases; SEACAT; SEACIT; Target of Rapamycin Complex 1 (TORC1); amino acid signaling; yeast