期刊
FEBS LETTERS
卷 586, 期 16, 页码 2239-2244出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2012.05.046
关键词
Tau; Alternative splicing; 9G8; PKA
资金
- Nantong University
- New York State Office for People With Developmental Disabilities
- National Natural Science Foundation of China [81030059, 30801202]
- Natural Science Foundation of Jiangsu [BK2009159]
- Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD)
- U.S. Alzheimer's Association [IIRG-10-173154]
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 alpha and beta 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.
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