Modulation of the membrane-binding projection domain of tau protein: Splicing regulation of exon 3

Meltem Cevik Arikan, John Memmott, Jennifer A. Broderick, Athena Andreadis, Athena Andreadis, Robert Lafyatis, Gavin Screaton, Stefan Stamm

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. The N-terminal domain of the protein interacts with the axonal membrane, and is modulated by differential inclusion of exons 2 and 3. These two tau exons are alternatively spliced cassettes, in which exon 3 never appears independently of exon 2. Previous work with tau minigene constructs indicated that exon 3 is intrinsically suboptimal and its primary regulator is a weak branch point. In this study, we confirm the role of the weak branch point in the regulation of exon 3 but also show that the exon is additionally regulated by a combination of exonic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 3 isoforms, Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 3.

Original languageEnglish
Pages (from-to)109-121
Number of pages13
JournalMolecular Brain Research
Issue number1-2
StatePublished - May 30 2002

Bibliographical note

Funding Information:
This work was supported by NIH RO1 grant NS38051 (A.A.), an Arthritis Foundation Medical Science Grant (R.L.), Deutsche Forschungsgemeinschaft SFB 473 (S.S.), and the Medical Research Council (G.S.). We want to thank our colleagues for their generous gifts of factor cDNAs: Drs. Joanne Yeakley and Javier Cáceres for ASF, James Patton for PTB, Benoit Chabot for hnRNPA1 and Christopher Smith for SV-αTM.


  • Alternative splicing
  • MAP tau
  • Membrane-interacting domain
  • Regulated isoform
  • cis and trans splicing regulator

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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