Delta-catenin-induced dendritic morphogenesis. An essential role of p190RhoGEF interaction through Akt1-mediated phosphorylation.
Delta-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 delta-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated delta-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of delta-catenin in this interaction. We have also found that delta-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. Delta-catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. Delta-catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, delta-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 delta-catenin-induced dendrogenesis and spine morphogenesis.
Kim
Hangun
H
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
Han
Jeong-Ran
JR
Park
Jaejun
J
Oh
Minsoo
M
James
Sarah E
SE
Chang
Sunghoe
S
Lu
Qun
Q
Lee
Kwang Youl
KY
Ki
Hyunkyoung
H
Song
Woo-Joo
WJ
Kim
Kwonseop
K
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003713:Dendritic Cells / Q000502:physiology*; D004622:Embryo, Mammalian; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013912:Threonine / Q000378:metabolism; D014162:Transfection; D020666:ras-GRF1 / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; C513037:Rasgrf1 protein, mouse; D020666:ras-GRF1; D013912:Threonine; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; D000095002:Delta Catenin