Glycogen synthase kinase-3 plays a crucial role in tau exon 10 splicing and intranuclear distribution of @entity5313 . Implications for XXXX .

@entity563 @entity13859 @entity179 @entity195 @entity5313 @entity9459 @entity369
@entity13859 , including @entity195 , are @entity179 in which tau protein accumulates as a consequence of alterations in its metabolism. At least three different types of alterations have been described; in some cases, an aberrant mRNA splicing of tau exon 10 occurs; in other cases, the disorder is a consequence of missense mutations and, in most cases, aberrant tau hyperphosphorylation takes place. Glycogen synthase kinase-3 (GSK-3) has emerged as a key kinase that is able to interact with several proteins involved in the etiology of @entity195 and other @entity13859 . Here, we have evaluated whether GSK-3 is also able to modulate tau-mRNA splicing. Our data demonstrate that GSK-3 inhibition in cultured neurons affects tau splicing resulting in an increase in tau mRNA containing exon 10. Pre-mRNA splicing is catalyzed by a multimolecular complex including members of the @entity563 / @entity369 -rich (SR) family of splicing factors. Immunofluorescence studies showed that after GSK-3 inhibition, @entity5313 , a member of the SR family, is redistributed and enriched in nuclear speckles and colocalizes with the kinase. Furthermore, immunoprecipitated @entity5313 is phosphorylated by recombinant @entity9459 . Phosphorylation of a peptide from the SR domain by GSK-3 revealed that the peptide needs to be prephosphorylated, suggesting the involvement of a priming kinase. Our results demonstrate that GSK-3 plays a crucial role in tau exon 10 splicing, raising the possibility that GSK3 could contribute to @entity13859 via aberrant tau splicing.
