Ypt/Rab GTPases regulate two intersections of the secretory and the endosomal/lysosomal pathways

Lipatova, Zhanna; Segev, Nava

doi:10.4161/21592780.2014.954870

Cited by 9 publications

(12 citation statements)

References 44 publications

(72 reference statements)

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“…This placement agrees with the established roles of Ypt1 and Ypt31 on the two sides of the Golgi (Lipatova et al, 2015). It also supports the idea that although Ypt/Rab GTPases can regulate multiple transport steps (Lipatova and Segev, 2014), they are specific to intracellular compartments (Zerial and McBride, 2001). …”

Section: Discussionsupporting

confidence: 76%

Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases

et al. 2016

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Current models entail that transport through the Golgi — the main sorting compartment of the cell — occurs via cisternal progression/maturation, and that Ypt/Rab GTPases regulate this process. However, there is very limited evidence that cisternal progression is regulated, and no evidence for involvement of Ypt/Rab GTPases in such a regulation. Moreover, controversy about the placement of two of the founding members of the Ypt/Rab family, Ypt1 and Ypt31, to specific Golgi cisternae interferes with addressing this question in yeast, where cisternal progression has been extensively studied. Here, we establish the localization of Ypt1 and Ypt31 to opposite faces of the Golgi, early and late, respectively. Moreover, we show that they partially overlap on a transitional compartment. Finally, we determine that changes in Ypt1 and Ypt31 activity affect Golgi cisternal progression, early-to- transitional and transitional-to-late, respectively. These results show that Ypt/Rab GTPases regulate two separate steps of Golgi cisternal progression.

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Section: Discussionsupporting

confidence: 76%

Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases

et al. 2016

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“…We have elucidated two examples for the second way: Ypt1 and Ypt31/Ypt32 coordinate the exocytic pathway with two different types of recycling processes, autophagy and PM recycling, respectively, each in the context of different modules (Lipatova and Segev, 2014). We proposed that Ypt1 coordinates early steps of the exocytic and the autophagic pathways, ER-to- Golgi and pre-autophagosomal structure (PAS) formation, respectively.…”

Section: New Paradigms Emerging From Current Yeast Ypt Studiesmentioning

confidence: 99%

“…It is possible that the same GEF stimulates Ypt31/Ypt32 in these two transport steps, which merge at the trans Golgi. However, it is possbile that there is a still an uncharacterized GEF for Ypt31/Ypt32 (Lipatova and Segev, 2014). …”

Section: New Paradigms Emerging From Current Yeast Ypt Studiesmentioning

confidence: 99%

“…The problem is that intracellular accumulation of the marker used for this study, GFP-tagged Snc1, can be caused by a defect either in endosome-to-Golgi transport or in autophagy. Using the best-characterized mutation from the Sclafani et al study and four rigorous assays, we recently established that this mutation confers an ER-autophagy and not a endosome-to-Golgi transport defect (Lipatova and Segev, 2014, Lipatova et al, 2013). Therefore, we consider Ypt1 as a regulator specific to dispatching cargo from the ER to the exocytic or autophagic pathways, and Ypt31/Ypt32 as trans-Golgi specific regulators that control transport to this compartment from endosomes, and from this compartment to the PM.…”

Section: Future Challengesmentioning

confidence: 99%

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Ypt/Rab GTPases: Principles learned from yeast

Lipatova

Hain

Nazarko

et al. 2015

Critical Reviews in Biochemistry and Molecular Biology

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Ypt/Rab GTPases are key regulators of all membrane trafficking events in eukaryotic cells. They act as molecular switches that attach to membranes via lipid tails to recruit their multiple downstream effectors, which mediate vesicular transport. Originally discovered in yeast as Ypts, they were later shown to be conserved from yeast to humans, where Rabs are relevant to a wide array of diseases. Major principles learned from our past studies in yeast are currently accepted in the Ypt/Rab field including: i) Ypt/Rabs are not transport-step specific, but are rather compartment specific, ii) stimulation by nucleotide exchangers, GEFs, is critical to their function, whereas GTP hydrolysis plays a role in their cycling between membranes and the cytoplasm for multiple rounds of action, iii) they mediate diverse functions ranging from vesicle formation to vesicle fusion, and iv) they act in GTPase cascades to regulate intracellular trafficking pathways. Our recent studies on Ypt1 and Ypt31/Ypt32 and their modular GEF complex TRAPP raise three exciting novel paradigms for Ypt/Rab function: (a) coordination of vesicular transport substeps, (b) integration of individual transport steps into pathways, and (c) coordination of different transport pathways. In addition to its amenability to genetic analysis, yeast provides a superior model system for future studies on the role of Ypt/Rabs in traffic coordination due to the smaller proteome that results in a simpler traffic grid. We propose that different types of coordination are important also in human cells for fine-tuning of intracellular trafficking, and that coordination defects could result in disease.

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“…These enzymes are associated to hepatocyte ER, the proliferation of ER usually occurs in the liver after being exposed to xenobiotics (Komatsu et al 2005; Yang et al 2016). Autophagy is known to be part of the ER quality control (ERQC) system via both micro-or macro-ER-phagy, using p62 as an adaptor or requiring core autophagy related proteins, respectively (Schuck et al 2014; Khaminets et al 2015; Ding and Yin 2008; Lipatova and Segev 2014, 2015; Lipatova et al 2013). Another common organellophagy is pexophagy, a type of autophagy that participates in the quality control of peroxisomes, which is important to lipid metabolism and hydrogen peroxide production and degradation (Nordgren et al 2013).…”

Section: Autophagy: the Basic Processmentioning

confidence: 99%

Relevance of autophagy to fatty liver diseases and potential therapeutic applications

et al. 2017

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Autophagy is an evolutionarily conserved lysosome-mediated cellular degradation program. Accumulating evidence shows that autophagy is important to the maintenance of liver homeostasis. Autophagy involves recycling of cellular nutrients recycling as well as quality control of subcellular organelles. Autophagy deficiency in the liver causes various liver pathologies. Fatty liver disease (FLD) is characterized by the accumulation of lipids in hepatocytes and the dysfunction in energy metabolism. Autophagy is negatively affected by the pathogenesis of FLD and the activation of autophagy could ameliorate steatosis, which suggests a potential therapeutic approach to FLD. In this review, we will discuss autophagy and its relevance to liver diseases, especially FLD. In addition we will discuss recent findings on potential therapeutic applications of autophagy modulators for FLD.

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Ypt/Rab GTPases regulate two intersections of the secretory and the endosomal/lysosomal pathways

Cited by 9 publications

References 44 publications

Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases

Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases

Ypt/Rab GTPases: Principles learned from yeast

Relevance of autophagy to fatty liver diseases and potential therapeutic applications

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