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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Gu J,Shi J,Wu S,Jin N,Qian W,Zhou J,Iqbal IG,Iqbal K,Gong CX,Liu F

doi

10.1016/j.febslet.2012.05.046

subject

Has Abstract

pub_date

2012-07-30 00:00:00

pages

2239-44

issue

16

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(12)00432-2

journal_volume

586

pub_type

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