Modulation of the membrane-binding domain of tau protein: splicing regulation of exon 2

Abstract

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 regulated 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 2 resembles a constitutive exon. In this study, we show that exon 2 is regulated by a combination of exonic and intronic enhancers and silencers. Furthermore, we demonstrate that known splicing regulators affect the ratio of exon 2 isoforms. Lastly, we tentatively pinpoint the site of action of several splicing factors which regulate tau exon 2.