The Roles of Monomeric GTP-Binding Proteins in Macroautophagy in Saccharomyces cerevisiae

Yang, Shu; Rosenwald, Anne G.

doi:10.3390/ijms151018084

Cited by 7 publications

(8 citation statements)

References 84 publications

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“…Previous work has elucidated roles for several monomeric GTP-binding proteins, 11 including some known to function in post-Golgi compartments, such as Ypt31-Ypt32 13 . In this study, we showed that 2 additional monomeric GTP-binding proteins that function in this area, Arl1 and Ypt6, also have roles in autophagy.…”

Section: Discussionsupporting

confidence: 50%

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Autophagy inSaccharomyces cerevisiaerequires the monomeric GTP-binding proteins, Arl1 and Ypt6

Yang

Rosenwald

2016

Autophagy

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Macroautophagy/autophagy is a cellular degradation process that sequesters organelles or proteins into a double-membrane structure called the phagophore; this transient compartment matures into an autophagosome, which then fuses with the lysosome or vacuole to allow hydrolysis of the cargo. Factors that control membrane traffic are also essential for each step of autophagy. Here we demonstrate that 2 monomeric GTP-binding proteins in Saccharomyces cerevisiae, Arl1 and Ypt6, which belong to the Arf/Arl/Sar protein family and the Rab family, respectively, and control endosome-trans-Golgi traffic, are also necessary for starvation-induced autophagy under high temperature stress. Using established autophagy-specific assays we found that cells lacking either ARL1 or YPT6, which exhibit synthetic lethality with one another, were unable to undergo autophagy at an elevated temperature, although autophagy proceeds normally at normal growth temperature; specifically, strains lacking one or the other of these genes are unable to construct the autophagosome because these 2 proteins are required for proper traffic of Atg9 to the phagophore assembly site (PAS) at the restrictive temperature. Using degron technology to construct an inducible arl1Δ ypt6Δ double mutant, we demonstrated that cells lacking both genes show defects in starvation-inducted autophagy at the permissive temperature. We also found Arl1 and Ypt6 participate in autophagy by targeting the Golgi-associated retrograde protein (GARP) complex to the PAS to regulate the anterograde trafficking of Atg9. Our data show that these 2 membrane traffic regulators have novel roles in autophagy.

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Section: Discussionsupporting

confidence: 50%

“…There is ample evidence, particularly in S. cerevisiae , that many membrane-traffic regulators, including several monomeric GTP-binding proteins are indispensable for autophagy 11 . Examples include the Rab protein family members Ypt1, Ypt31-Ypt32 and Ypt7, 12-14 and the Arf/Arl/Sar family members Arf1-Arf2 and Sar1 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Autophagy inSaccharomyces cerevisiaerequires the monomeric GTP-binding proteins, Arl1 and Ypt6

Yang

Rosenwald

2016

Autophagy

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“…No systematic study has been undertaken of all the GTPase proteins in even a simple unicellular organism like S. cerevisiae, although it is clear several members of the Arf/Arl/Sar and Ypt/Rab families are required for construction of the autophagosome and for fusion of the autophagosome with the vacuole. 4,23,24 Members of the Rac/Rho/Cdc42 family, proteins generally viewed as regulators of cell polarity and cytoskeletal function, also appear to have signaling roles in autophagy. 25,26 Interestingly, RhoA along with its downstream effector, ROCK1 appears to mediate switching between autophagy and apoptosis via control of Beclin-1 (the ortholog of Atg6 in S. cerevisiae) levels in mammalian cells.…”

Section: Future Directionsmentioning

confidence: 99%

“…Finally, small GTPases of the Arf/Arl/Sar and Rab families are required for both construction of the autophagosome and fusion of the autophagosome with the lysosome (or vacuole in yeast) in a variation of their roles as membrane traffic regulators for the secretory pathway and endocytosis. [4][5][6][7] In this Commentary, we will describe our recent work documenting roles for 2 GTPases in macroautophagy, Arl1, a member of the Arf/ Arl/Sar family of small GTPases, and Ypt6, a member of the Rab family, in S. cerevisiae, 8 describe how these data fit into a larger understanding of the roles of membrane traffic in macroautophagy, then discuss future directions. We will focus primarily on what has been learned from studies in yeast, but note that this process is highly conserved across eukaryotes, including higher plants and animals.…”

Section: Introductionmentioning

confidence: 99%

Small GTPase proteins in macroautophagy

Yang

Rosenwald

2016

Small GTPases

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Macroautophagy, a highly conserved process in eukaryotic cells, is initiated in response to stress, especially nutrient starvation. Macroautophagy helps cells survive by engulfing proteins and organelles into an unusual double-membraned structure called the autophagosome, which then fuses with the lysosome. Upon degradation of the engulfed contents, the building blocks are recycled for synthesis of new macromolecules. Recent work has demonstrated that construction of the autophagosome requires a variety of small GTPases in variations of their normal roles in membrane traffic. In this Commentary, we review our own recent findings with respect to 2 different GTPases, Arl1, a member of the Arf/Arl/Sar family, and Ypt6, a member of the Rab family, in the yeast S. cerevisiae in light of other information from the literature and discuss future directions for further discerning the roles of small GTPases in autophagy.

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“…Susan and Peter [5] tried to analyse the role of GTP-binding proteins in transport along the exocytic pathway. Moreover, Yang and Rosenwald [3] summarized the functions of the monomeric GTP-binding proteins in macroautophagy in Saccharomyces cerevisiae. For the role of GTP binding sites in membrane trafficking, there are many researchers focusing on this field.…”

Section: Introductionmentioning

confidence: 99%

Incorporating efficient radial basis function networks and significant amino acid pairs for predicting GTP binding sites in transport proteins

2016

BMC Bioinformatics

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BackgroundGuanonine-protein (G-protein) is known as molecular switches inside cells, and is very important in signals transmission from outside to inside cell. Especially in transport protein, most of G-proteins play an important role in membrane trafficking; necessary for transferring proteins and other molecules to a variety of destinations outside and inside of the cell. The function of membrane trafficking is controlled by G-proteins via Guanosine triphosphate (GTP) binding sites. The GTP binding sites active G-proteins initiated to membrane vesicles by interacting with specific effector proteins. Without the interaction from GTP binding sites, G-proteins could not be active in membrane trafficking and consequently cause many diseases, i.e., cancer, Parkinson… Thus it is very important to identify GTP binding sites in membrane trafficking, in particular, and in transport protein, in general.ResultsWe developed the proposed model with a cross-validation and examined with an independent dataset. We achieved an accuracy of 95.6% for evaluating with cross-validation and 98.7% for examining the performance with the independent data set. For newly discovered transport protein sequences, our approach performed remarkably better than similar methods such as GTPBinder, NsitePred and TargetSOS. Moreover, a friendly web server was developed for identifying GTP binding sites in transport proteins available for all users.ConclusionsWe approached a computational technique using PSSM profiles and SAAPs for identifying GTP binding residues in transport proteins. When we included SAAPs into PSSM profiles, the predictive performance achieved a significant improvement in all measurement metrics. Furthermore, the proposed method could be a power tool for determining new proteins that belongs into GTP binding sites in transport proteins and can provide useful information for biologists.

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The Roles of Monomeric GTP-Binding Proteins in Macroautophagy in Saccharomyces cerevisiae

Cited by 7 publications

References 84 publications

Autophagy inSaccharomyces cerevisiaerequires the monomeric GTP-binding proteins, Arl1 and Ypt6

Autophagy inSaccharomyces cerevisiaerequires the monomeric GTP-binding proteins, Arl1 and Ypt6

Small GTPase proteins in macroautophagy

Incorporating efficient radial basis function networks and significant amino acid pairs for predicting GTP binding sites in transport proteins

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