The proteolytic landscape of the yeast vacuole

Hecht, Karen A.; O’Donnell, Allyson F.; Brodsky, Jeffrey L.

doi:10.4161/cl.28023

Cited by 95 publications

(88 citation statements)

References 141 publications

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“…(b)]. Although as a whole vacuolar proteases are thought to have very broad substrate specificity, particular proteases may be more substrate specific . However, these results have been obtained using synthetic substrates and therefore may not hold in vivo in yeast.…”

Section: Resultsmentioning

confidence: 99%

Sequence-based analysis of protein degradation rates

2017

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Protein turnover is a key aspect of cellular homeostasis and proteome dynamics. However, there is little consensus on which properties of a protein determine its lifetime in the cell. In this work, we exploit two reliable datasets of experimental protein degradation rates to learn models and uncover determinants of protein degradation, with particular focus on properties that can be derived from the sequence. Our work shows that simple sequence features suffice to obtain predictive models of which the output correlates reasonably well with the experimentally measured values. We also show that intrinsic disorder may have a larger effect than previously reported, and that the effect of PEST regions, long thought to act as specific degradation signals, can be better explained by their disorder. We also find that determinants of protein degradation depend on the cell types or experimental conditions studied. This analysis serves as a first step towards the development of more complex, mature computational models of degradation of proteins and eventually of their full life cycle. Proteins 2017; 85:1593-1601. © 2017 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%

Sequence-based analysis of protein degradation rates

2017

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“…This is consistent with mutants affected in V-ATPase proton pumping, such as stv1 Δ, vph1 Δ, and erg2Δ mutants, not inducing the full range of phenotypes observed in other autophagy mutants; particularly, reduced survival under nitrogen starvation conditions, ineffective aminopeptidase I processing or reduced activity in the modified alkaline phosphatase Pho8Δ60p assay. The latter two proteins rely on proteolysis by Prb1p for activation [65], an event occurring in the vacuolar lumen. Prb1p itself undergoes a series of proteolytic modifications en route to the vacuole, being finally processed in the lumen by Pep4p in a luminal low pH dependent manner [64].…”

Section: Discussionmentioning

confidence: 99%

8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae

Hernández¹,

Serrano-Bueno²,

Perez-Castiñeira³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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8-Dehydrosterols are present in a wide range of biologically relevant situations, from human rare diseases to amine fungicide-treated fungi and crops. However, the molecular bases of their toxicity are still obscure. We show here that 8-dehydrosterols, but not other sterols, affect yeast vacuole acidification through V-ATPases. Moreover, erg2Δ cells display reductions in proton pumping rates consistent with ion-transport uncoupling in vitro. Concomitantly, subunit Vph1p shows conformational changes in the presence of 8-dehydrosterols. Expression of a plant vacuolar H(+)-pumping pyrophosphatase as an alternative H(+)-pump relieves Vma(-)-like phenotypes in erg2Δ-derived mutant cells. As a consequence of these acidification defects, endo- and exo-cytic traffic deficiencies that can be alleviated with a H(+)-pumping pyrophosphatase are also observed. Despite their effect on membrane traffic, 8-dehydrosterols do not induce endoplasmic reticulum stress or assembly defects on the V-ATPase. Autophagy is a V-ATPase dependent process and erg2Δ mutants accumulate autophagic bodies under nitrogen starvation similar to Vma(-) mutants. In contrast to classical Atg(-) mutants, this defect is not accompanied by impairment of traffic through the CVT pathway, processing of Pho8Δ60p, GFP-Atg8p localisation or difficulties to survive under nitrogen starvation conditions, but it is concomitant to reduced vacuolar protease activity. All in all, erg2Δ cells are autophagy mutants albeit some of their phenotypic features differ from classical Atg(-) defective cells. These results may pave the way to understand the aetiology of sterol-related diseases, the cytotoxic effect of amine fungicides, and may explain the tolerance to these compounds observed in plants.

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“…In higher eukaryotes, retromer recycles the cargo receptor VPS10/sortilin from endosomes to the Golgi [63], [64]. This cargo receptor is a transmembrane protein which target soluble proteins, such as CPY, pro-proteinase A and Aminopeptidase Y, to the vacuole in yeast [65]. In recent studies, homologues of VPS10 have been described in T. gondii and P. falciparum [62], [66].…”

Section: Endosomal Factors Involved In the Biogenesis Of Secretory Ormentioning

confidence: 99%

Vacuolar protein sorting mechanisms in apicomplexan parasites

Jiménez-Ruiz

Morlon-Guyot

Daher

et al. 2016

Molecular and Biochemical Parasitology

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The phylum Apicomplexa comprises more than 5000 species including pathogens of clinical and economical importance. These obligate intracellular parasites possess a highly complex endomembrane system to build amongst others three morphologically distinct secretory organelles: rhoptries, micronemes and dense granules. Proteins released by these organelles are essential for invasion and hijacking of the host cell. Due to the complexity of the internal organization of these parasites, a wide panoply of trafficking factors was expected to be required for the correct sorting of proteins towards the various organelles. However, Toxoplasma gondii and other apicomplexan parasites contain only a core set of these factors and several of the vacuolar protein sorting (VPS) homologues found in most eukaryotes have been lost in this phylum.In this review, we will summarise our current knowledge about the role of trafficking complexes in T. gondii, highlighting recent studies focused on complexes formed by VPS proteins. We also present a novel, hypothetical model, suggesting the recycling of parasite membrane and micronemal proteins.

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The proteolytic landscape of the yeast vacuole

Cited by 95 publications

References 141 publications

Sequence-based analysis of protein degradation rates

Sequence-based analysis of protein degradation rates

8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae

Vacuolar protein sorting mechanisms in apicomplexan parasites

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