Figure 5. Regulation of Rac1 activity via “signalosome” of DISC1/Kal-7.
(a) Inhibition of Rac1 activity (level of GTP-Rac1) by DISC1-FL (red asterisk), but not DISC1-ΔKal-7, and augmentation of the activity by DISC1 knockdown (green asterisk) in primary cortical neurons. Augmented Rac1 activity is also monitored by phosphorylation of Pak1. Full-length blots are presented in Supplementary Fig. 18. (b) Decreased Rac1/Kal-7 binding by DISC1-FL (red asterisk), not by DISC1-ΔKal-7. (c) Key role of Rac1 in DISC1-regulated spine enlargement, as evident by its blockade by expression of Rac1-DN (dominant-negative). Scale bar, 20 μm. Bar, s.e.m. Significant effects of Rac1-DN compared to mock are shown as *P < 0.05, †P < 0.01, #P < 0.001. Full-length blots are presented in Supplementary Fig. 18.