Lipid Rafts And Caveolae Are Essential For IGF-1 Receptor Signaling During 3T3-L1 Preadipocyte Differentiation Induction

Lipid rafts and 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 and caveolae of the plasma membrane and can directly interact with caveolin-1, the major protein component in caveolae. Disruption of lipid rafts and caveolae by depleting cellular cholesterol with cholesterol-binding reagent, β-methylcyclodextrin or filipin, blocks the IGF-1 receptor signaling in 3T3-L1 preadipocyte. Both hormone induced adipocyte differentiation and mitotic clonal expansion are inhibited by lipid rafts and caveolae disruption. However, a nonspecific lipid binding reagent, xylazine, does not affect adipocyte differentiation or mitotic expansing. Further studies indicate that lipid rafts and caveolae are required only for IGF-1 receptor downstream signaling and not the activation of receptoritself by ligand. Thus, our results suggest that localization in lipid rafts and caveolae and association with caveolin enable IGF-1 receptor to have a close contact with downstream signal molecules recruited into lipid rafts and caveolae and transmit the signal through these signal molecule complexes.