Abstract

The Saccharomyces cerevisiae lysosome-like vacuole is a useful model for studying membrane fusion events and organelle maturation processes utilized by all eukaryotes. The vacuolar membrane is capable of forming micrometer and nanometer scale domains that can be visualized using microscopic techniques and segregate into regions with surprisingly distinct lipid and protein compositions. These lipid raft domains are liquid-ordered (Lo) like regions that are rich in sphingolipids, phospholipids with saturated acyl chains, and ergosterol. Recent studies have shown that these lipid rafts contain an enrichment of many different proteins that function in essential activities such as nutrient transport, organelle contact, membrane trafficking, and homotypic fusion, suggesting that they are biologically relevant regions within the vacuole membrane. Here, we discuss recent developments and the current understanding of sphingolipid and ergosterol function at the vacuole, the composition and function of lipid rafts at this organelle and how the distinct lipid and protein composition of these regions facilitates the biological processes outlined above.

Highlights

  • The lysosomal vacuole of S. cerevisiae plays a number of important roles in cellular homeostasis

  • This study utilized Laurdan spectroscopy experiments to measure the anisotropy and movement of the dye within the membrane, and the results suggested that the formation of these domains depended on the presence of C26-phytosphingolipid species due their disappearance from giant unilamellar vesicles (GUVs) when the lipids were isolated from elo3 or sur2 yeast

  • Most sphingolipid biosynthetic genes display varying levels of interactions with genes annotated as having a function in membrane trafficking and endolysosomal maturation

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Summary

INTRODUCTION

The lysosomal vacuole of S. cerevisiae plays a number of important roles in cellular homeostasis. The fungal vacuole is necessary for nutrient storage, protein turnover, and detoxification, but it plays a large and often-underappreciated role in essential processes such as autophagy, ion homeostasis, and organelle contact and fusion (Li and Kane, 2009). Through years of exemplary work by a number of labs across the world many of the factors that are necessary for fusion have been identified, and in most cases a molecular mechanism for these effectors has been investigated in detail. These fusion effectors include proteins such as tethers, Rab/Rho GTPases, SNAREs, chaperones and actin, and the regulatory lipids phosphatidic acid (PA), diacylglycerol (DAG), ergosterol, and phosphatidylinositol phosphates (PtdInsPs), which. In this review we highlight research that has focused on this subject and discuss outstanding questions and future perspectives related to it

SPHINGOLIPIDS IN MEMBRANE TRAFFICKING AND ENDOSOMAL MATURATION
ERGOSTEROL AND RAFT DOMAINS
CONCLUSION AND FUTURE PERSPECTIVES
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