Guenebeaud et al., 2010 - The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Molecular Cell   40(6):863-876 Full text @ Mol. Cell

Fig. 7

PP2A Is Involved in UNC5H2 Proapoptotic Signaling during Angiogenesis

(A) UNC5H2, DAPk, and PR65β siRNA silencing by siRNA are associated with a decrease in caspase-3 activity in HUAEC endothelial cells. Results are means ± SEM. (n = 3). All p values are < to 0.03 (U test).

(B) Silencing of PR65β using specific morpholinos rescues vascular defects induced by netrin-1a silencing in fli:eGFP zebrafish embryos. PR65β morpholinos rescue the effect of netrin-1 withdrawal-induced defects, abolished by injection of PR65β mRNAs. Intersegmental vessel (ISV) presence was analyzed at 30 hr gestation. Representative images of morpholino-injected zebrafish embryos are shown for each condition. Percentage of zebrafish with ISV defect is indicated (p < 0.001, Khi-2 test).

(C) PR65β silencing reduces caspase-3 activation induced by netrin-1a silencing in zebrafish embryos. Injection of PR65β mRNAs suppress this effect. Results are means ± SEM of caspase-3 activity (n = 3; p < 0.02, Student′s t test).

(D) Model of PR65β/PP2A and CIP2A implication in DAPk-mediated UNC5H2-induced apoptosis. In the presence of netrin-1, the UNC5H2 receptor adopts a closed conformation and interacts with an inactive, phosphorylated form of DAPk. Phosphorylation of DAPk is maintained by CIP2A, which interacts with UNC5H2 and inhibits PP2A. In the absence of netrin-1, UNC5H2 adopts an open conformation and recruits PR65β/PP2A into an UNC5H2-DAPk complex. PR65β/PP2A recruitment leads to DAPk dephosphorylation and activation, and thus to apoptosis induction.

ZFIN wishes to thank the journal Molecular Cell for permission to reproduce figures from this article. Please note that this material may be protected by copyright. Full text @ Mol. Cell