Pathological Role of Peptidyl-Prolyl Isomerase Pin1 in the Disruption of Synaptic Plasticity in Alzheimer’s Disease

Figure 1

Pin1 proteins exist in detergent-resistant dendritic rafts and PSD fractions coincidently containing phosphorylated Tau, oligomers of Aβ, and glutamate receptor. The detergent-resistant synaptosome suspension was fractionated by sucrose gradient ultracentrifugation to isolate dendritic rafts and PSDs. (a) Analysis of dendritic rafts. Proteins in ultracentrifuged fractions at equal volume were analyzed by Western blot or dot blot. Fraction 4 contained flotillin and GM1 ganglioside, known markers for rafts, along with Pin1, p-Tau, oligomers of Aβ, Shank3, and NR1 proteins. Fraction 4 did not show calnexin, a marker of endoplasmic reticulum (ER). (b) Analysis of the PSD. PSD proteins at equal amounts were analyzed by Western blot or dot blot. PSD95 and Shank3, both known protein markers of the PSD, were enriched in the PSD fraction (PSD2), along with Pin1, NR1, p-Tau, and oligomers of Aβ. Ctrl: human control tissues; AD: human AD tissues; T: total tissue; P1: total membrane; NR1: a subunit of NMDA receptor; Syn: synaptosome; PSD1: pellets from the synaptosome treated once by 0.5% Triton X-100; PSD2: pellets from PSD1 treated once more by 0.5% Triton X-100.

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