神经细胞中胰岛素样生长因子Ⅰ受体在胞膜窖的定位

Localization of Insulin-like Growth Factor I Receptor in Caveolae of Neuronal Cells

胰岛素样生长因子I(insulin-like growth factor-I,IGF-I)是调节神经生长的一种重要活性物质。胞膜窖(caveolae)是细胞膜上富含胆固醇的微结构域,作为结构平台为某些神经营养因子的信号转导所需。本文研究了IGF-I在神经细胞中与胞膜窖的关系。IGF-I对嗜铬细胞瘤细胞株PC12的神经保护作用被methyl-β-cyclodextrin(CD)所导致的细胞胆固醇水平的降低所抑制。免疫荧光染色实验证明IGF-I受体定位于PC12的胞膜窖中,CD的添加破环了IGF-I在胞膜窖中的定位。鼠神经细胞的原代培养研究进一步证实IGF-I在神经细胞中的抗细胞凋亡作用与细胞胆固醇含量有关,而小脑颗粒细胞原代培养的研究证明无论在细胞体还是在神经突起部分IGF-I受体均定位于其胞膜窖中。所有这些结果证明IGF-I受体定位于神经细胞的细胞窖中,其生理功能的发挥需要细胞窖的参与。

Insulin-like growth factor-Ⅰ （IGF-Ⅰ） is the important factor which regulates the growth of neuron. Caveolae, cholesterol-rich microdomains of plasma membrane, act as platforms for some neurotrophic factors. In this study, we examined the relationship of IGF-Ⅰ to caveolae in neuronal cells. The neuronprotective action of IGF-Ⅰ was inhibited by the methyl-β-cyclodextrin （CD）-induced cholesterol depletion in pheochromocytoma PC12 cells. Immunocytochemical analysis demonstrated that CD destroyed the localization of IGF-Ⅰ receptor in caveolae. IGF-Ⅰ receptor was localized in caveolae; treatment of The primary culture of neuron further shown that the anti-apoptotic role of IGF-Ⅰ was also involved in cholesterol content. Cerebellum granules neuron culture demonstrated that IGF-Ⅰ receptor was localized in both soma and neutrite parts of neuron. Taken together, our results demonstrated that IGF-Ⅰ receptor was localized in caveolae of neuron which was required for the neuroprotective action of IGF-Ⅰ.