中文摘要：

Tau外显子10的可变剪接产生含3个微管结合片段或4个微管结合片段的tau蛋白变异体（3R-tau和4R-tau）.正常成年人脑中,3R-tau和4R-tau的表达水平相近,这种比例对于维持正常脑功能非常重要.9G8是剪接因子SR蛋白家族中的成员之一,参与多种基因转录产物的剪接调控,它的功能和活性受磷酸化高度调节.糖原合酶激酶（GSK）-3β是体内重要的蛋白激酶,已有研究显示它参与调节tau外显子10的可变剪接.利用微型tau基因研究了9G8在不同细胞系中对tau外显子10可变剪接的作用以及GSK-3β对9G8介导的tau外显子10可变剪接的影响.结果显示,过表达9G8抑制tau外显子10的表达,GSK-3β在体外可催化9G8的磷酸化,GSK-3β可以被9G8从大鼠脑匀浆中沉降（pull-down）,提示它们之间可能存在相互作用,在培养的细胞中,GSK-3β与9G8之间存在共定位,过表达GSK-3β抑制9G8对外显子10可变剪接的作用,有利于4R-tau的产生.这些结果显示GSK-3β影响9G8介导的tau外显子10的剪接.

英文摘要：

Alternative splicing of tau exon 10 generates tau isoforms with 3 or 4 microtubule-binding repeats.In normal adult human brain,approximately equal levels of 3R-tau and 4R-tau are expressed,which is required for maintaining normal brain functions.9G8,one member of SR protein family,is involved in the splicing of many genes.The function of 9G8 is highly regulated by the phosphorylation.It was reported that GSK-3β regulates the alternative splicing of tau exon 10.Mini-tau gene were used to study the regulation of 9G8 on tau exon 10 splicing and the effect of GSK-3β on 9G8-mediated tau exon 10 splicing.It was found that 9G8 inhibited the inclusion of tau exon 10.GSK-3β phosphorylated 9G8 in vitro and interacted with 9G8.Overexpression of GSK-3β inhibited 9G8-mediated tau exon 10 inclusion.