Department of Biochemistry and Molecular Biology, Medical School, Soochow University, 199 Renai Road, Soochow, Jiangsu 215123, China.
FEBS Lett. 2012 Jul 30;586(16):2239-44. doi: 10.1016/j.febslet.2012.05.046. Epub 2012 Jun 4.
Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, named 3R- or 4R-tau. Normal adult human brain expresses equal levels of them. Imbalance of 3R-tau and 4R-tau associates with several tauopathies. Splicing factor 9G8 suppresses tau exon 10 inclusion and its function is regulated by phosphorylation. Here, we found that cyclic AMP-dependent protein kinase (PKA) phosphorylated 9G8. The catalytic subunits α and β of PKA interacted with 9G8, and activation of PKA enhanced the interaction. Up-regulation of PKA activity prevented 9G8 from inhibition of tau exon 10 inclusion. These findings provide novel insights into the regulation of tau exon 10 splicing and further our understanding of neurodegeneration associated with dysregulation of tau exon 10 splicing.
外显子 10 的 tau 剪接产生具有三个或四个微管结合重复的 tau 同工型，分别命名为 3R-或 4R-tau。正常成人脑中表达它们的水平相等。3R-tau 和 4R-tau 的失衡与几种 tau 病有关。剪接因子 9G8 抑制 tau 外显子 10 的包含，其功能受磷酸化调节。在这里，我们发现环腺苷酸依赖性蛋白激酶（PKA）磷酸化了 9G8。PKA 的催化亚基 α 和 β 与 9G8 相互作用，PKA 的激活增强了相互作用。PKA 活性的上调阻止了 9G8 抑制 tau 外显子 10 的包含。这些发现为 tau 外显子 10 剪接的调节提供了新的见解，并进一步加深了我们对与 tau 外显子 10 剪接失调相关的神经退行性变的理解。
