SRPK2 promotes tau hyperphosphorylation. A, Depletion of SRPK2 reduces tau S214 phosphorylation in APP/PS1 DG. Immunohistochemical staining of tau S214 phosphorylation was performed in LV-GFP or LV-shSRPK2 virus infected DG in WT or APP/PS1 mice. Examples of cells showing positive signal were indicated by arrows. Scale bar, 50 μm. B, Depletion of SRPK2 reduces apoptosis in APP/PS1 DG. Immunohistochemical staining of active caspase 3 was performed in LV-GFP or LV-shSRPK2 virus infected DG of WT or APP/PS1 mice. Examples of cell showing positive signal were indicated by arrows. Scale bar, 25 μm. C, Depletion of SRPK2 reduces the amount of PHF-tau in APP/PS1 DG. Immunohistochemical staining of PHF-tau using AT8 antibody was performed in LV-GFP or LV-shSRPK2 virus infected DG of WT or APP/PS1 mice. Examples of cell showing positive signal were indicated by arrows. Scale bar, 50 μm. D, Overexpression of SRPK2 promotes tau aggregation in primary neurons. Primary rat neurons (DIV10) were infected with LV-GFP, LV-myc-SRPK2, or LV-SRPK2-KD for 48 h. The amount of tau in different cellular fractions were separated by ultracentrifugation, detected by Western blot analysis, and densitometrically quantified (first panel, p < 0.05, Student's t test, n = 3). Expressions of various SRPK2 mutants (fourth panel), cytosolic tau (second panel), aggregated tau (third panel), and tubulin (fifth panel) were also examined.