Pike L J, Miller J M
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 1998 Aug 28;273(35):22298-304. doi: 10.1074/jbc.273.35.22298.
Caveolae and detergent-insoluble, glycosphingolipid-enriched domains (DIGs) are cholesterol-enriched membrane domains that have been implicated in signal transduction because a variety of signaling proteins as well as phosphatidylinositol bisphosphate (PtdInsP2) are compartmentalized in these domains. We report here that depletion of cellular cholesterol leads to the inhibition of epidermal growth factor- and bradykinin-stimulated PtdIns turnover in A431 cells. This is associated with the loss of compartmentalization of epidermal growth factor receptors, Gq, and PtdInsP2 in the low density membrane domains. Replacement of cellular cholesterol leads to the reorganization of signaling molecules in the low density domains and the reestablishment of hormone-stimulated PtdIns hydrolysis. Oxysterol derivatives show a variable ability to functionally replace the cholesterol in this system. These data are consistent with the hypothesis that localization of signaling proteins and lipids to cholesterol-enriched domains is required for the proper function of hormone-stimulated PtdIns turnover.
小窝和去污剂不溶性、富含糖鞘脂的结构域（DIGs）是富含胆固醇的膜结构域，由于多种信号蛋白以及磷脂酰肌醇二磷酸（PtdInsP2）在这些结构域中被分隔开来，因此它们与信号转导有关。我们在此报告，细胞胆固醇的耗竭会导致A431细胞中表皮生长因子和缓激肽刺激的PtdIns周转受到抑制。这与低密度膜结构域中表皮生长因子受体、Gq和PtdInsP2的分隔丧失有关。细胞胆固醇的补充导致低密度结构域中信号分子的重新组织以及激素刺激的PtdIns水解的重新建立。氧甾醇衍生物在该系统中显示出不同的功能替代胆固醇的能力。这些数据与以下假设一致，即信号蛋白和脂质定位于富含胆固醇的结构域是激素刺激的PtdIns周转正常功能所必需的。
