δ-Catenin-induced Dendritic Morphogenesis
AN ESSENTIAL ROLE OF p190RhoGEF INTERACTION THROUGH AKT1-MEDIATED PHOSPHORYLATION*
- Hangun Kim‡,1,
- Jeong-Ran Han‡,1,
- Jaejun Park§,
- Minsoo Oh‡,
- Sarah E. James¶,
- Sunghoe Chang§,
- Qun Lu¶,
- Kwang Youl Lee‡,
- Hyunkyoung Ki‡,
- Woo-Joo Song∥ and
- Kwonseop Kim‡,2
- ‡College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea, the §Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea, the ¶Department of Anatomy and Cell Biology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, and the ∥Graduate Program in Neuroscience and Institute for Brain Science and Technology, Inje University, Daejeon 614-735, Korea
- ↵2 To whom correspondence should be addressed: College of Pharmacy, Chonnam National University, Bldg. 1-211, 300 Yongbong-dong, Gwangju 500-757, Korea. Tel.: 82-62-530-2937; Fax: 82-62-530-2949; E-mail: koskim{at}chonnam.ac.kr.
Abstract
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 mushroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of δ-catenin-induced dendrogenesis and spine morphogenesis.
- Received August 27, 2007.
- Revision received November 5, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
