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Role of caveolae in the adipocyte's lipid droplet regulation

Ziel

The storage of triacylglycerols so as to provide energy for the organism in case of food deprivation is amajor function of adipocytes. In addition, the adipose tissue contains the largest body pool of free-cholesterol localized in the lipid droplet. Moreover, the adipose tissue constitutes the highest expressing tissue of caveolinswhich are known to act as cholesterol-binding proteins. We propose to try to find out if the dynamics of thesecaveolins, that have recently been reported to be around lipid droplets, could be implicated in the transport/storage of cholesterol to the lipid droplets. For this purpose, we will follow the distribution of cholesterol analogy like filliping and dehydroergsoterolduring the time-course of 3T3-L1 adiposities and co localize it with specific adiposity markers tagged with fluorescent protein. Besides, by using [3H] photo cholesterol, it will be possible to cross-link proteins interacting directly with cholesterol. In order to know if cavalla dynamics could influence cholesterol trafficking, we will study the consequences of an over expression of capelins on cholesterol distribution and cholesterol efflux. To establish the physiological relevance of capelins in cholesterol trafficking, we will try to find out if caveolin-1null mice generated in the host lab (Drab et al, 2001) are resistant to high fat diet as reported for another strain. What is more, in vitro differentiation of these preadipocytes will give us a physiological model of knock-outcaveolin-1 in fat cells to study the effect on cholesterol distribution. Then, we will analyse the effect of adownregulation of capelins on cholesterol distribution by using Kenai in 3T3-L1 adiposities. In parallel, overexpression of different parts of cave Olin tagged with fluorescent proteins will be achieved in order to determine the effect on cholesterol localization. Finally, we propose to study the consequences of a down regulation of Niemann Pick C-I (NPC1) by RNAi, #

Wissenschaftliches Gebiet (EuroSciVoc)

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Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-5
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

EIF - Marie Curie actions-Intra-European Fellowships

Koordinator

MAX PLANCK GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V. REPRESENTED BY THE MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS, DRESDEN
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