Functional Implications of Glycogen Synthase Kinase-3-Mediated Tau Phosphorylation

Figure 1

Tau isoforms in the human CNS and identified GSK-3 phosphorylation sites. The diagram illustrates the six isoforms of tau present in the human CNS. The longest tau isoform includes alternatively spliced exons 2, 3, and 10. Exons 2 and 3 encode two short amino acid inserts near the N-terminus of the molecule (1N and 2N, respectively). Exclusion of exons 2 and 3 gives rise to 0N tau isoforms, inclusion of exon 2 produces 1N tau isoforms, and inclusion of exons 2 and 3 results in the expression of 2N tau isoforms. Exon 10 encodes an additional microtubule-binding repeat domain (R2) that is present in 4R, but absent from 3R, tau isoforms. The number of amino acids in each tau isoform is indicated on the right. The centre of the molecule comprises a proline-enriched region that harbours the majority of the identified GSK-3 phosphorylation sites in 2N4R tau. Serine (S) and threonine (T) residues that have been identified as being phosphorylated by GSK-3 in vitro are indicated below.