Reconstruction of gene association network reveals a transmembrane protein required for adipogenesis and targeted by PPARγ.
We have developed a method for reconstructing gene association networks and have applied this method to gene profiles from 3T3-L1 cells. Priorization of the candidate genes pinpointed a transcript annotated as APMAP (adipocyte plasma membrane-associated protein). Functional studies showed that APMAP is upregulated in murine and human adipogenic cell models as well as in a genetic mouse model of obesity. Silencing APMAP in 3T3-L1 cells strongly impaired the differentiation into adipocytes. Moreover, APMAP expression was strongly induced by the PPARγ ligand rosiglitazone in adipocytes in vitro and in vivo in adipose tissue. Using ChIP-qPCR and luciferase reporter assays, we show a functional PPARγ binding site. In addition, we provide evidence that the extracellular C-terminal domain of APMAP is required for the function of APMAP in adipocyte differentiation. Finally, we demonstrate that APMAP translocates from the endoplasmatic reticulum to the plasma membrane during adipocyte differentiation.
Bogner-Strauss
Juliane G
JG
Institute for Genomics and Bioinformatics, Graz University of Technology, Petersgasse 14, 8010 Graz, Austria. juliane.bogner-strauss@tugraz.at
Prokesch
Andreas
A
Sanchez-Cabo
Fatima
F
Rieder
Dietmar
D
Hackl
Hubert
H
Duszka
Kalina
K
Krogsdam
Anne
A
Di Camillo
Barbara
B
Walenta
Evelyn
E
Klatzer
Ariane
A
Lass
Achim
A
Pinent
Montserrat
M
Wong
Wing-Cheong
WC
Eisenhaber
Frank
F
Trajanoski
Zlatko
Z
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics*; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
C439388:APMAP protein, mouse; D008562:Membrane Glycoproteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins