Fig. 1

Proteomics and phosphoproteomics of dorsal hippocampal CA1 (dCA1) and ventral hippocampal CA1 (vCA1) in P301L mice. a Representative images showing abundant hyper-phosphorylated tau (p-Tau, AT8) in the vCA1 but not in the dCA1 of 3-month-old male P301L mice. Scale bar = 500 μm (vHP) or 200 μm (dHP). b Radar graph depicting differentially expressed proteins in the vCA1 (left) or dCA1 (right) between P301L mice and WT mice. From the outside to the inside, the first circle represents the name of protein. The orange arrow in the second circle represents the sequence of the differentially expressed proteins according to their P-values, arranged from smallest to largest. The third circle represents the ratio of differential expression changes in the comparison groups, namely, P301L^vCA1 vs. WT^vCA1 and P301L^dCA1 vs. WT^dCA1, with log₂ transformation. In this representation, the colour pink indicates upregulation, while blue denotes down-regulation. The size of the data point corresponds to the magnitude of the difference. The fourth circle represents the average quantitative value of the two groups. c Heatmap displaying the functional enrichment clusters of differentially expressed proteins and phosphorylated proteins according to biological function. d Volcano plot of phosphoproteomic data revealing changes in the levels of phosphorylated proteins in P301L^vCA1 vs. WT^vCA1 and P301L^dCA1 vs. WT^dCA1. The red and blue dots represent phosphorylated proteins whose abundance significantly increased and decreased, respectively. n = 3 per group. ^*P < 0.05; ^**P < 0.01; ^***P < 0.001. WT wild type, vDG ventral dentate gyrus, dDG dorsal dentate gyrus, SERPINA3K serine protease inhibitor A3K, SERPINA3N serine protease inhibitor A3N, ADI1 1,2-dihydroxy-3-keto-5-methylthiopentene dioxygenase, LVD isovaleryl-CoA dehydrogenase, TAGLN transgelin, HDHD3 haloacid dehalogenase-like hydrolase domain-containing protein 3, SERPINA1A serine protease inhibitor A1A, TTR transthyretin, GABRA3 γ-aminobutyric acid receptor subunit alpha-3, FGA fibrinogen alpha chain, HDDC3 guanosine-3’,5’-bis (diphosphate) 3’-pyrophosphohydrolase MESH1, IGKC immunoglobulin kappa constant, GABRA2 γ-aminobutyric acid receptor subunit alpha-2, ALAD delta-aminolevulinic acid dehydratase, TRPM5 transient receptor potential cation channel subfamily M member 5, MYH11 myosin-11, FABP7 fatty acid-binding protein type 7, SERPINA1E serine protease inhibitor A1E, NRGN neurogranin, TUBB2B tubulin beta-2B, ME3 NADP-dependent malic enzyme, RAB3B ras-related protein Rab-3B, D2HGDH D-2-hydroxyglutarate dehydrogenase, CALB2 calretinin, FBLN5 fibulin-5, MAPT microtubule-associated protein tau, NME3 nucleoside diphosphate kinase 3, MPST mercaptopyruvate sulfurtransferase, SUGP2 SURP and G-patch domain-containing protein 2, NNT nicotinamide nucleotide transhydrogenase, TMEM254C transmembrane protein 254c, CD109 CD109 antigen, P01864 Ig gamma-2A chain C region, BCAS1 breast carcinoma-amplified sequence 1 homolog, D2HGDH D-2-hydroxyglutarate dehydrogenase, ITPKA inositol-trisphosphate 3-kinase A, MAP9 microtubule-associated protein 9, SASH1 SAM and SH3 domain-containing protein 1, ARHGEF2 Rho guanine nucleotide exchange factor 2, CAMKIIa calcium/calmodulin-dependent protein kinase type II subunit alpha, TRAF3IP3 TNF receptor-associated factor interacting protein 3, PCLO protein piccolo, TMEM38A trimeric intracellular cation channel type A, ARHGEF28 rho guanine nucleotide exchange factor 28, MMP20 matrix metalloproteinase-20, ERICH5 glutamate-rich protein 5, S serine, T threonine