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- W60886235 abstract "The protein and lipid composition of eukaryotic plasma membranes is highly dynamicand regulated according to need. Despite its great plasticity, the plasma membraneretains some organizational features, such as its lateral organization into distinctdomains. In the yeast, Saccharomyces cerevisiae, large immobile protein clusters,termed eisosomes, are important for plasma membrane organization. Eisosomeshelp to sort proteins into discrete domains, function in endocytosis and are implicatedin cellular signaling. The major eisosome components Pil1 and Lsp1 were firstidentified as in vitro targets of the sphingolipid long chain base-regulated Pkhkinases.However, it is not known if eisosomes are targets of Pkh-mediatedsphingolipid signaling in vivo. In this thesis, I show that Pkh-kinases regulateeisosome formation in response to alterations of complex sphingolipid levels in theplasma membrane. I found that Pkh-kinase-dependent phosphorylation of Pil1controls the assembly state of eisosomes. The combination of different unbiased,global analysis methods, such as proteomics and high content screening enabled meto identify Nce102 as a negative regulator of Pkh-kinases. Nce102 relocalizesbetween MCC domains, overlaying eisosomes, and the remainder of the plasmamembrane in response to alterations in sphingolipid levels. Together with itsregulatory function on Pkh-kinases that localize at eisosomes, this relocalizationsuggests that it is part of a sphingolipid sensor. Furthermore, I identified Rom2, aRho1 GTPase exchange factor, as a novel regulator of sphingolipid metabolism. Mydata reveal several new insights into regulation of sphingolipid metabolism andplasma membrane organization. I provide a model how a homeostatic feedback loopmay control sphingolipid levels. This likely will help in understanding how cells adjustprocesses, such as eisosome driven domain organization, endocytosis and actinorganization to altered conditions. Furthermore, I anticipate that the datasets createdin this thesis will serve as a resource for future studies on plasma membranefunction." @default.
- W60886235 created "2016-06-24" @default.
- W60886235 creator A5071883928 @default.
- W60886235 date "2010-08-13" @default.
- W60886235 modified "2023-09-27" @default.
- W60886235 title "Analysis of sphingolipid-signaling at the plasma membrane of Saccharomyces cerevisiae" @default.
- W60886235 hasPublicationYear "2010" @default.
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