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  • In the body the brain is the most cholesterol rich organ. Despite this, remarkably little is known about the mechanisms in the brain that regulate cholesterol homeostasis. By screening for T3 regulated genes we have identified Disp3, a sterol-sensing domain containing protein. DISP3 localizes within the endoplasmic reticulum and was further found to co-localize with cholesterol. Ectopic expression of DISP3 in fibroblasts resulted in elevated cholesterol levels combined with an altered cholesterol distribution. Currently, it is unknown what is responsible for the alteration of cholesterol in cells with modulated DISP3 expression and whether this protein interacts directly with cholesterol or other lipids. During the proposed project we will attempt to further characterize the function of DISP3 with regards to the regulation of cholesterol homeostasis and to study the potential physical interaction between DISP3 and cholesterol by in vitro and in vivo methods. In addition, we will establish the importance of the sterol-sensing domain for modulating cellular cholesterol distribution. (en)
  • Přestože mozek obsahuje značné množství cholesterolu, je poměrně málo známo o mechanismech jeho regulace v tomto orgánu. Při hledání nových genů, které jsou regulovány thyroidním hormonem jsme identifikovali Disp3, nového člena SSD (sterol-sensing domain) proteinové rodiny. Vnitrobuněčně se DISP3 nachází v oblasti endoplazmatického retikula, kde kolokalizuje s cholesterolem. Ektopická exprese DISP3 ve fibroblastech vede k relokalizaci a k akumulaci celkového cholesterolu v buňce. V současné době není známo co způsobuje změnu cholesterolu v buňkách s modulovanou expresí DISP3 a zda DISP3 interaguje přímo s cholesterolem či s jinými lipidy. V předkládaném projektu chceme dále charakterizovat funkci DISP3 v homeostáze buněčného cholesterolu a dále pak studovat přímou interakci mezi DISP3 proteinem a cholesterolem, popřípadě dalšími steroly, a to pomocí in vitro a in vivo metod. Dále bychom rádi objasnili úlohu SSD-domény, popřípadě dalších domén, v této interakci.
Title
  • The role of DISP3 protein in lipid metabolism (en)
  • Úloha proteinu DISP3 v lipidovém metabolismu
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  • GAP301/12/1478
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  • sterol-sensing domain cholesterol lipids metabolism (en)
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