Treatment of neurons with antibody 22C11 causes apoptosis and DNA synthesis and expression of C57 or C31 causes neuronal apoptosis and DNA synthesis. A, Sustained treatment of neurons with 1 μl/ml of 22C11, a ligand mimetic for APP, causes neuronal apoptosis. Expression of either myc-PAK3-K297R or peptide myc-PAK3 (101-126) significantly abrogates 22C11-mediated neuronal apoptosis. Significant differences were confirmed by ANOVA (F(6,62) = 28.0; p < 0.0001). Post hoc t tests done using the Bonferroni multiple comparisons test reveal significant differences between the following groups: 22C11 or 22C11+lac versus 22C11+mycPAK3K297R, 22C11+mycPAK3 (101-126), 22C11 versus lac (no 22C11), mock (no 22C11) or 9E10 (p < 0.001 for all comparisons). B, Sustained treatment of cortical neurons with 22C11 leads to a significant increase in the number of neurons showing DNA synthesis. Significant differences were confirmed by ANOVA (F(5,53) = 95.4; p < 0.0001). Post hoc t tests done using the Bonferroni multiple comparisons test reveal significant differences between the following groups: 22C11 (1 μl) or 22C11 (2 μl) versus 9E10 (1 μl), 9E10 (2 μl), lac, or mock (p < 0.001 for all comparisons), and 22C11 (1 μl) versus 22C11 (2 μl) (p < 0.01). All other relevant comparisons were NS. C, Infection of neurons with HSV vectors expressing myc-tagged C57 or C31 causes an increase in the number of apoptotic nuclei relative to infection of neurons with control HSV-Lac. Coexpression of dominant-negative PAK3 or addition of PTX causes a significant reduction in the number of apoptotic nuclei in cultures expressing myc-C57 or myc-C31. Significant differences were confirmed by ANOVA (F(8,81) = 34.95; p < 0.0001). Post hoc t tests done using the Bonferroni multiple comparisons test reveal significant differences between the following groups: mycC57 versus mycC57+mycPAK3K297R, mycC57+PTX or lac, and mycC31 versus mycC31+mycPAK3K297R, mycC31+PTX or lac (p < 0.001 for all comparisons). Other relevant comparisons were NS. D, Expression of myc-tagged C57 or C31 leads to a significant increase in the number of neurons showing DNA synthesis. Significant differences were confirmed by ANOVA (F(3,36) = 12.98; p < 0.0001). Post hoc t tests done using the Bonferroni multiple comparisons test demonstrated a significant increase in the number of BrdU-positive nuclei in cultures infected with HSV-myc-C57 or HSV-myc-C31 versus lac or mock (p < 0.001). Other relevant comparisons were NS.