Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in <i>S. cerevisiae</i>

Phelan, John P.; Millson, Stefan H.; Parker, Peter J.; Piper, Peter W.; Cooke, Frank T.

doi:10.1242/jcs.03188

Cited by 21 publications

(19 citation statements)

References 56 publications

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“…AP-1 is involved in traffic between the TGN and endosomes and Yap180p acts in endocytosis. Interestingly, both Apl4p and Yap180p interact with the Fab1p complex subunit Vac14p [33] and deletion of Apl4p reduces the levels of PI(3,5)P 2 [93]. Furthermore, overexpression of Fab1p can rescue sorting defects caused by inactivation of AP-1.…”

Section: Resultsmentioning

confidence: 99%

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Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae

Michaillat

Mayer

2013

PLoS ONE

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The equilibrium of membrane fusion and fission influences the volume and copy number of organelles. Fusion of yeast vacuoles has been well characterized but their fission and the mechanisms determining vacuole size and abundance remain poorly understood. We therefore attempted to systematically characterize factors necessary for vacuole fission. Here, we present results of an in vivo screening for deficiencies in vacuolar fragmentation activity of an ordered collection deletion mutants, representing 4881 non-essential genes of the yeast Saccharomyces cerevisiae. The screen identified 133 mutants with strong defects in vacuole fragmentation. These comprise numerous known fragmentation factors, such as the Fab1p complex, Tor1p, Sit4p and the V-ATPase, thus validating the approach. The screen identified many novel factors promoting vacuole fragmentation. Among those are 22 open reading frames of unknown function and three conspicuous clusters of proteins with known function. The clusters concern the ESCRT machinery, adaptins, and lipases, which influence the production of diacylglycerol and phosphatidic acid. A common feature of these factors of known function is their capacity to change membrane curvature, suggesting that they might promote vacuole fragmentation via this property.

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Section: Resultsmentioning

confidence: 99%

“…Second, the effects of AP-1 mutations on vacuole fragmentation might be due to altered PI(3,5)P 2 levels. This appears likely because Apl4p and Yap180 interact with Vac14p [33] and because Δapl4 cells show reduced levels of PI(3,5)P 2 [93]. Furthermore, overexpression of FAB1 can rescue sorting defects caused by inactivation of AP-1.…”

Section: Resultsmentioning

confidence: 99%

Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae

Michaillat

Mayer

2013

PLoS ONE

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“…As vacuole fission dynamics remain unchanged upon ENV7 deletion, and as ENV7 overexpression leads to increased fragmentation, Env7 appears to act as an inhibitor of membrane fusion and remodeling. The absence of defects in vacuole fission and acidification suggests that Env7 functions independently of the phosphoinositol-regulated vacuole fission events orchestrated by the vacuolar membrane complex of lipid kinase Fab1, lipid phosphatase Fig4, and the scaffolding protein Vac14 (35,63,(79)(80)(81)(82)(83)(84)(85)(86)(87).…”

Section: Discussionmentioning

confidence: 99%

Saccharomyces cerevisiae Env7 Is a Novel Serine/Threonine Kinase 16-Related Protein Kinase and Negatively Regulates Organelle Fusion at the Lysosomal Vacuole

Manandhar

Ricarte

Cocca

et al. 2013

Molecular and Cellular Biology

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Membrane fusion depends on conserved components and is responsible for organelle biogenesis and vesicular trafficking. Yeast vacuoles are dynamic structures analogous to mammalian lysosomes. We report here that yeast Env7 is a novel palmitoylated protein kinase ortholog that negatively regulates vacuolar membrane fusion. Microscopic and biochemical studies confirmed the localization of tagged Env7 at the vacuolar membrane and implicated membrane association via the palmitoylation of its N-terminal Cys13 to -15. In vitro kinase assays established Env7 as a protein kinase. Site-directed mutagenesis of the Env7 alanineproline-glutamic acid (APE) motif Glu269 to alanine results in an unstable kinase-dead allele that is stabilized and redistributed to the detergent-resistant fraction by interruption of the proteasome system in vivo. Palmitoylation-deficient Env7C13-15S is also kinase dead and mislocalizes to the cytoplasm. Microscopy studies established that env7⌬ is defective in maintaining fragmented vacuoles during hyperosmotic response and in buds. ENV7 function is not redundant with a similar role of vacuolar membrane kinase Yck3, as the two do not share a substrate, and ENV7 is not a suppressor of yck3⌬. Bayesian phylogenetic analyses strongly support ENV7 as an ortholog of the gene encoding human STK16, a Golgi apparatus protein kinase with undefined function. We propose that Env7 function in fusion/fission dynamics may be conserved within the endomembrane system.

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“…This recycling process is assumed to occur through vesicular-tubular transport intermediates like those induced by clathrin, adaptor proteins and retromer (Currinn et al, 2016;de Lartigue et al, 2009;Ho et al, 2012;Phelan et al, 2006), but remains speculative. This type of membrane fission is distinct from "kiss-and-run" process, where lysosomes undertake transient homotypic and heterotypic fusion events that are followed by fission to avoid coalescence of lysosomes (Bright et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence

Choy

Saffi

Wallace

et al. 2018

Preprint

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Summary statementPIKfyve inhibition causes lysosomes to coalesce, resulting in fewer, enlarged lysosomes. We also show that TFEB-mediated lysosome biosynthesis does not contribute to swelling.. CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/295246 doi: bioRxiv preprint first posted online Apr. 5, 2018; 2 AbstractLysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function.

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Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiae

Cited by 21 publications

References 56 publications

Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae

Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae

Saccharomyces cerevisiae Env7 Is a Novel Serine/Threonine Kinase 16-Related Protein Kinase and Negatively Regulates Organelle Fusion at the Lysosomal Vacuole

Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence

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