The Journal of Neuroscience, February 9, 2005, ():
Presenilin Attenuates Receptor-Mediated Signaling and Synaptic Function
J. Neurosci. Parent et al.
25: 1540
Supplemental data
Files in this Data Supplement:
- supplemental material
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Figure 1S. Lack of PS function increases spine density, PSD-95 and DCC clusters. Representative 3D reconstruction of confocal images of cortical neurons. PSD-95 and DCC staining are shown respectively for Wt (top panel) and Wt neurons treated with Compound E (bottom panel). Synaptic clusters of PSD-95 (green) and DCC (red) are visualized as yellow overlay (left panel).
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Figure 2S. mEPSC amplitude in PS-deficient neurons. Amplitude of mEPSC events is analyzed from cortical pyramidal neurons. mEPSC events (above noise) are shown using a 5 min epoch (n=9, n=7 and n=7 embryos for Wt, KO, PS inhibitor, respectively). The cumulative probability of mEPSC amplitude events is analyzed in basal condition (a), before and after application of FSK in Wt (b), KO (c) and PS inhibitor treated (d) neurons. Statistical analysis was performed using a two-way ANOVA followed by Scheffé post-hoc analysis. *p<0.05 compared to Wt; #p<0.05 compared to basal.
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Figure 3S. Analysis of synaptic structure in PS-deficient neurons. (a) Steady-state levels of PSD-95 is examined in detergent lysates of 12-19 DIV cortical neurons by Western blot analysis using monoclonal PSD-95 antibody (a1) and quantified from 3 independent cultures (a2). (b) PSD-95 immunofluorescence staining is evaluated from fixed cultured neurons. The number of PSD-95 clusters (b2) and total staining intensity expressed as relative value compared to Wt group (b1) are examined. (c) Cluster intensity of Bassoon (c1) and PSD-95 (c2) staining are shown and expressed as intensity per pixel. (d) Representative confocal images of enlarged dendritic area of cortical neurons immunostained with GluR2 antibody are shown respectively for Wt (d1) and KO (d2) neurons.
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Figure 4S. Model of synaptic regulation by PS-dependent proteolysis of DCC. Lack of PS function reduces the intramembraneous proteolysis of DCC, which leads to the accumulation of membrane-tethered DCC intracellular domain. DCC transmembrane domain may serve as an anchor that facilitates recruitment of signaling proteins to DCC intracellular domain in a manner that exacerbates phosphorylation of substrates downstream of cAMP/PKA activation pathway. Increase of cAMP/PKA cascade will lead to a more efficient presynaptic release, which can be also associated with strengthening of the synapse at the postsynaptic site.
