Cyclic AMP-dependent protein kinase regulates 9G8-mediated alternative splicing of tau exon 10

详细信息    查看全文

• 作者：Jianlan Gu ; Jianhua Shi ; Shiliang Wu ; Nana Jin ; Wei Qian ; Jianhua Zhou ; Inge-Grundke Iqbal ; Khalid Iqbal ; Cheng-Xin Gong ; Fei Liu
• 关键词：Tau ; Alternative splicing ; 9G8 ; PKA
• 刊名：FEBS Letters
• 出版年：2012
• 出版时间：30 July, 2012
• 年：2012
• 卷：586
• 期：16
• 页码：2239-2244
• 全文大小：952 K

文摘

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 ¦Á and ¦Â 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.

Structured summary of protein interactions

with by coimmunoprecipitation ()