Cyclic AMP-dependent protein kinase regulates 9G8-mediated alternative splicing of tau exon 10.
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.
Department of Biochemistry and Molecular Biology, Medical School, Soochow University, 199 Renai Road, Soochow, Jiangsu 215123, China.
Jianlan
J
Gu
Jianhua
J
Shi
Shiliang
S
Wu
Nana
N
Jin
Wei
W
Qian
Jianhua
J
Zhou
Inge-Grundke
IG
Iqbal
Khalid
K
Iqbal
Cheng-Xin
CX
Gong
Fei
F
Liu
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D020134:Catalytic Domain; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D005091:Exons; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000737:chemistry; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics*; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors; D015854:Up-Regulation; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics*
C054369:MAPT protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D016875:tau Proteins; D000068103:Serine-Arginine Splicing Factors; D017868:Cyclic AMP-Dependent Protein Kinases