Transfer of the glycosylphosphatidylinositol-anchored 5'-nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis.
OBJECTIVE
In addition to predominant localization at detergent-insoluble, glycolipid-enriched plasma membrane microdomains (DIGs), glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-proteins) have been found associated with lipid droplets (LDs) and adiposomes. Adiposomes are vesicles that are released from adipocytes in response to anti-lipolytic and lipogenic signals, such as H(2)O(2), palmitate and the antidiabetic sulfonylurea drug, glimepiride, and harbour (c)AMP-degrading GPI-proteins, among them the 5-nucleotidase CD73. Here the role of adiposomes in GPI-protein-mediated information transfer was studied.


METHODS
Adiposomes were incubated with isolated rat adipocytes under various conditions. Trafficking of CD73 and lipid synthesis were analysed.


RESULTS
Upon blockade of GPI-protein trafficking, CD73 specifically associated with DIGs of small, and to a lower degree, large, adipocytes. On reversal of the blockade, CD73 appeared at cytosolic LD in time- adiposome concentration- and signal (H(2)O(2) > glimepiride > palmitate)-dependent fashion. The salt- and carbonate-resistant association of CD73 with structurally intact DIGs and LD was dependent on its intact GPI anchor. Upon incubation with small and to a lower degree, large adipocytes, adiposomes increased lipid synthesis in the absence or presence of H(2)O(2), glimepiride and palmitate and improved the sensitivity toward these signals. Upregulation of lipid synthesis by adiposomes was dependent on the translocation of CD73 with intact GPI anchors from DIGs to LD.


CONCLUSIONS
The signal-induced transfer of GPI-anchored CD73 from adiposomes via DIGs to LD of adipocytes mediates paracrine upregulation of lipid synthesis within the adipose tissue.
Müller
G
G
Sanofi-Aventis Germany GmbH, Research & Development, Therapeutic Department Metabolism, Frankfurt am Main, Germany. guenter.mueller@sanofi-aventis.com
Jung
C
C
Wied
S
S
Biemer-Daub
G
G
Frick
W
W
D015720:5'-Nucleotidase / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D019899:Paracrine Communication; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D013997:Time Factors; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D013453:Sulfonylurea Compounds; D019308:Palmitic Acid; C057619:glimepiride; D006861:Hydrogen Peroxide; D015720:5'-Nucleotidase; C548243:Nt5e protein, rat