Fig. 5: Phosphoproteomics of Akap11 mutant synapses shows hyperphosphorylation of PKA substrates. | Nature Communications

Fig. 5: Phosphoproteomics of Akap11 mutant synapses shows hyperphosphorylation of PKA substrates.

From: Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder

Fig. 5

a Number of phosphoproteins reaching a significance threshold of nominal P < 0.05. Fractions of upregulated and downregulated DAPPs are highlighted in red and blue, respectively. b Volcano plots of 12wk synapse phosphoproteomics data for Akap11+/- and Akap11-/- vs. WT controls. Phosphoproteomic measurements are normalized to MS-proteomics measurements from the same samples. Known PKA Cα substrates from PhosphoSitePlus are labeled green. AKAP11 phosphopeptides are omitted from Akap11-/- plots, for clarity. a,b A moderated two-sample t-test was applied to the datasets to compare WT, Akap11+/- and Akap11-/- sample groups. c Motif analysis of peptides flanking the phosphorylation site of P < 0.05 phosphosites in A. n(fg) are the number of foreground peptides, and n(bg) are the number of background peptides. Red lines indicate FDR significance, calculated by log odds enrichment. d PTM-SEA of synapse phosphoproteomics data, using known kinase substrates from PhosphoSitePlus. Black borders indicate FDR significance. e ELISA-based PKA activity measurements comparing total lysate and synapse fractions of cortex (left) and striatum-enriched tissue (right). One Unit (U) is defined by the manufacturer as the quantity of PKA that catalyzes the transfer of 1.0 pmol phosphate from ATP to substrate. Two-way ANOVA with Tukey’s post hoc test. f Immunoblotting and quantification of AKAP11, PKA subunits, p-GluA1S845 and GluA1 in 12wk cortical total lysate. One-way ANOVA with Tukey’s post hoc test. e,f Data are represented as mean ± SEM. See Supplementary Data 1 for detailed statistical information.

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