δ-Catenin-induced Dendritic Morphogenesis: AN ESSENTIAL ROLE OF p1 90RhoGEF INTERACTION THROUGH AKT1 -MEDIATED PHOSPHORYLATION.

δ-Catenin was first identified through its interaction with Presenilin- 1 and has been implicated in the regulation of dendrogenesis and cognitive function. However, the molecular mechanisms by which δ-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated δ-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of δ-catenin in this interaction. We have also found that δ-catenin overexpression decreased the binding between p190RhoGEF and RhoA, and significantly lowered the levels of GTP-RhoA but not those of GTP-Rac1 and -Cdc42. δ-Catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. δ-Catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, δ-catenin T454A significantly reduced the length and number of mature mushsroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of δ-catenin- induced dendrogenesis and spine morphogenesis. [ABSTRACT FROM AUTHOR]