在发育过程中神经元前体细胞的外向迁移对于大脑皮层的多层结构建立有着重要作用.金属蛋白酶家族的成员ADAM17(A Disintegrin And Metalloprotease 17)对于多种膜蛋白的成熟释放有着重要作用,包括多个表皮生长因子受体的配体以及Notch等蛋白.这些底物中有多个对神经干细胞的增殖、分化、迁移都有重要作用.为了探讨ADAM17在大脑皮层发育过程中的生理作用,结合RNAi和IUE的技术,降低小鼠大脑发育阶段中ADAM17的表达.结果显示:用RNAi降低ADAM17在小鼠大脑皮层发育14—18d中的表达,会造成神经元前体细胞的外向迁移障碍,使得细胞停留在脑室下区.
The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 receptor is enriched in lipid rafts,which are membrane microdomains essential in signaling processes.One of those signaling processes is ADAM17-and ADAM10-dependent ectodomain shedding.By using an alkaline phosphatase tagged substrate reporter system,we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not;and overexpression of sigma-1 receptor diminished ADAM17-and ADAM10-dependent shedding.Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
Juan LiBin LiuXiaofei GaoZhixing MaTianyi CaoSongYan-ai MeiYufang Zheng
