Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors

Annette M. Hartmann, Dan Rujescu, Thomas Giannakouros, Eleni Nikolakaki, Michel Goedert, Eva Maria Mandelkow, Qing Sheng Gao, Athena Andreadis, Stefan Stamm

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Tau is a microtubule-associated protein whose transcript undergoes regulated splicing in the mammalian nervous system. Exon 10 of the gene is an alternatively spliced cassette that is adult-specific and encodes a microtubule-binding domain. Mutations increasing the inclusion of exon 10 result in the production of tau protein which predominantly contains four microtubule-binding repeats and were shown to cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Here we show that exon 10 usage is regulated by CDC2-like kinases CLK1, 2, 3, and 4 that phosphorylate serine-arginine-rich proteins, which in turn regulate pre-mRNA splicing. Cotransfection experiments suggest that CLKs achieve this effect by releasing specific proteins from nuclear storage sites. Our results show that changing pre-mRNA-processing pathways through phosphorylation could be a new therapeutic concept for tauopathies.

Original languageEnglish
Pages (from-to)80-90
Number of pages11
JournalMolecular and Cellular Neuroscience
Issue number1
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by the Max Planck Society (S.S., E.M.), the DFG (Sta399/3-1) and the Johannes and Frieda Marohn Stiftung (Sta/00) (both to S.S.), NIH Grant Ro1-AG18486 to A.A. and the UK Medical Research Council.

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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