L: [email protected] authors declare no competing financial interest.ACKNOWLEDGMENTS The research was supported by the NIH (CA135380 and AA0197461) and the INGEN grant from the Lilly Endowment, Inc. (SOM). Computer time on the Big Red supercomputer at Indiana University is funded by the National Science Foundation and by Shared University Research grants from IBM, Inc., to Indiana University.
ReviewReviewCellular Logistics 4, e28023; March; 2014 Landes BioscienceThe proteolytic landscape of the yeast vacuoleKaren A Hecht1,, Allyson F O’Donnell2 and Jeffrey L Brodsky1,*Department of Biological Sciences; University of Pittsburgh; Pittsburgh, PA USA; 2Department of Cell Biology; University of Pittsburgh School of Medicine; Pittsburgh, PA USACurrent affiliation: Marine Biotechnology; Pacific Northwest National Laboratory; Sequim, wA USAKeywords: protease, S. cerevisiae, hydrolysis, autophagy, endocytosis, metalloprotease, Vps10, CPY, secretory pathway, PffThe vacuole in the yeast Saccharomyces cerevisiae plays a number of essential roles, and to provide some of these required functions the vacuole harbors at least seven distinct proteases. These proteases exhibit a range of activities and different classifications, and they follow unique paths to arrive at their ultimate, common destination in the cell. This review will first summarize the major functions of the yeast vacuole and delineate how proteins are targeted to this organelle. we will then describe the specific trafficking itineraries and activities of the characterized vacuolar proteases, and outline select features of a new member of this protease ensemble. Finally, we will entertain the question of why so many proteases evolved and reside in the vacuole, and what future research challenges exist in the field.Structure, Function, and Protein Trafficking Itineraries Associated with the Vacuole in the Yeast Saccharomyces cerevisiaeThe vacuole in most yeasts can occupy 20 of cell volume.Tarlatamab It is functionally similar to the plant vacuole and the lysosome in higher eukaryotes, with an important role in the degradation of macromolecules, nutrient storage, protein homeostasis, and detoxification.1,2 This organelle was first described in the 1930s from light microscopy images of plant cells showing large “empty” (vacuus, in Latin) structures within the cytosol.Givosiran 3 The vacuole in yeast is host to numerous proteases, lipases, nucleases, and transporters,1,4,5 and is a dynamic organelle that undergoes fusion and fission events in response to the cell cycle and environmental cues.PMID:23849184 Logarithmically growing cells have a multi-lobed vacuole, while in stationary phase cells, or cells starved of a carbon source, these lobes fuse to produce a single spherical vacuolar structure.6 The vacuole is also a slightly acidic environment (pH 6.2) compared with the cytosol (pH 7.2) in logarithmically growing yeast.7,8 In the remainder of this review, we will refer to “yeast” to indicate the organism Saccharomyces cerevisiae, unless otherwise indicated.*Correspondence to: Jeffrey L Brodsky; Email: [email protected] Submitted: 11/12/13; Revised: 01/27/14; Accepted: 01/28/14 Citation: Hecht KA, O’Donnell AF, Brodsky JL. The proteolytic landscape of the yeast vacuole. Cellular Logistics 2014; 4:e28023; http://dx.doi.org/10.4161/ cl.A host of proteins define the function of this organelle. Approximately 200 of the 6,000 yeast genes are annotated as encoding proteins having vacuolar localization, and 27 of th.