Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction.
Lipid rafts/caveolae are found to be essential for insulin-like growth factor (IGF)-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction. In 3T3-L1 cells, IGF-1 receptor is located in lipid rafts/caveolae of the plasma membrane and can directly interact with caveolin-1, the major protein component in caveolae. Disruption of lipid rafts/caveolae by depleting cellular cholesterol with cholesterol-binding reagent, beta-methylcyclodextrin or filipin, blocks the IGF-1 receptor signaling in 3T3-L1 preadipocyte. Both hormonal induced adipocyte differentiation and mitotic clonal expansion are inhibited by lipid rafts/caveolae disruption. However, a nonspecific lipid binding reagent, xylazine, does not affect adipocyte differentiation or mitotic clonal expansion. Further studies indicate that lipid rafts/caveolae are required only for IGF-1 receptor downstream signaling and not the activation of receptor itself by ligand. Thus, our results suggest that localization in lipid rafts/caveolae and association with caveolin enable IGF-1 receptor to have a close contact with downstream signal molecules recruited into lipid rafts/caveolae and transmit the signal through these signal molecule complexes.
Huo
Hairong
H
State Laboratory of Molecular Biology and Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Guo
Xuemin
X
Hong
Shangyu
S
Jiang
Manrong
M
Liu
Xinyuan
X
Liao
Kan
K
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D021941:Caveolae / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D008055:Lipids / Q000502:physiology*; D051379:Mice; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction
D008055:Lipids; D002784:Cholesterol; D017526:Receptor, IGF Type 1