Fig. 8

Proteomic analysis reveals potential regulators of Tau phosphorylation modulated by Pyk2. A–D, Synaptosomal fractions were prepared from hippocampi of 12-month-old WT and Pyk2^−/− animals and run through LC-MS/MS to identify proteins that are significantly differentially regulated by Pyk2 expression. A, Heat map showing relative abundance of significantly differentially regulated (p < 0.05) synaptic proteins between WT and Pyk2^−/− animals. B, Volcano plot of all total synaptic proteins identified via LC-MS/MS. Positive values for Log₂FC represent protein upregulation in Pyk2^−/− compared to WT. Dashed line represents p = 0.05. Significantly differentially regulated synaptic proteins shown in red. C, Heat map showing relative abundance of significantly differentially regulated (p < 0.05), phospho-enriched, synaptic proteins (normalized to total protein abundance) between WT and Pyk2^−/− animals. D, Volcano plot of all normalized, phospho-enriched, synaptic proteins identified via LC-MS/MS. Positive values for Log₂FC represent protein upregulation in Pyk2^−/− compared to WT. Dashed line represents p = 0.05. Significantly differentially regulated, synaptic phospho-proteins shown in red. Proximate regulators of Tau shown in blue. E, STRING protein-protein interaction network of all significantly differentially regulated, normalized, phospho-enriched, synaptic proteins. The interaction network was supplemented with MAPT (in red) to identify regulators of Tau. Proximate regulators of Tau (in blue) were defined as kinases or phosphatases positioned one or two degrees from MAPT. 6 kinases (and 0 phosphatases) were identified as proximate regulators of Tau modulated by Pyk2