Insulin-like growth factor-1 receptor signaling in 3T3-L1 adipocyte differentiation requires lipid rafts but not caveolae.
Previously, we have found that lipid rafts/caveolae were essential for insulin-like growth factor-1 (IGF-1) receptor signaling during 3T3-L1 preadipocytes differentiation induction. However, it was not identified as to which of the membrane lipid-ordered microdomains mediates the receptor signal. Using small double-stranded RNA-mediated interference (RNAi), we successfully suppressed the caveolin-1 protein expression. In cells stably transfected with vector expressing small interfering RNA (siRNA) fragment, no caveolin-1 protein or caveola was detected. On the other hand, removal of caveolin-1 did not affect the caveolinless lipid rafts or the localization of IGF-1 receptor in lipid rafts on plasma membrane. IGF-1 receptor signal transduction and induced cellular differentiation were normal in RNAi cells with only lipid rafts. Furthermore, these IGF-1 receptor signaling events were still sensitive to the cholesterol-binding reagents. Thus, our results suggest that lipid rafts are sufficient for IGF-1 receptor signaling and the recruitment of signal molecules by caveolin-1 is not essential for IGF-1 receptor signaling.
Hong
S
S
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
Huo
H
H
Xu
J
J
Liao
K
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D021941:Caveolae / Q000502:physiology* / Q000648:ultrastructure; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002454:Cell Differentiation; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006028:Glycosphingolipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D005456:Fluorescent Dyes; D006028:Glycosphingolipids; D034741:RNA, Small Interfering; D002784:Cholesterol; D017526:Receptor, IGF Type 1; D016650:Fluorescein-5-isothiocyanate