Protein Phosphatase 1 dephosphorylatesTDP‐43 and suppresses its function in tau exon 10 inclusion

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Transactive responseDNA‐binding protein of 43 kDa (TDP‐43) regulatesRNAprocessing, including alternative splicing of tau exon 10. PathologicalTDP‐43 is hyperphosphorylated. However, how do the protein phosphatase(s) (PP) regulateTDP‐43 phosphorylation is unclear. Here, we found that bothPP1 andPP2A were coimmunoprecipitated withTDP‐43. Treatment with calyculin A, but not with okadaic acid, increasedTDP‐43 phosphorylation at Ser379, Ser403/404, and Ser409/410 in cultured cells.PP1α,PP1β, andPP1γ interacted withTDP‐43. Overexpression ofPP1α andPP1γ, but notPP1β, suppressedTDP‐43 phosphorylation at Ser403/404 and Ser409/410 andTDP‐43‐induced tau exon 10 inclusion. These findings suggest thatPP1α andPP1γ regulateTDP‐43 phosphorylation and its function in tau exon 10 inclusion mainly through its phosphorylation at Ser403/404 and Ser409/410.
Funding Information
  • Nantong University
  • National Natural Science Foundation of China (31671046)

This publication has 33 references indexed in Scilit: