GSK-3β Modulates 9G8-mediated Alternative Splicing of Tau Exon 10

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-3 beta 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-3 beta on 9G8-mediated tau exon 10 splicing. It was found that 9G8 inhibited the inclusion of tau exon 10. GSK-3 beta phosphorylated 9G8 in vitro and interacted with 9G8. Overexpression of GSK-3 beta inhibited 9G8-mediated tau exon 10 inclusion.