Delta-catenin-induced dendritic morphogenesis. An essential role of p190RhoGEF interaction through Akt1-mediated phosphorylation

J Biol Chem. 2008 Jan 11;283(2):977-87. doi: 10.1074/jbc.M707158200. Epub 2007 Nov 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • Catenins
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Line
  • Delta Catenin
  • Dendritic Cells / physiology*
  • Embryo, Mammalian
  • GTP Phosphohydrolases / metabolism
  • Hippocampus / embryology
  • Mice
  • Morphogenesis / physiology*
  • Neurons / physiology
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Threonine / metabolism
  • Transfection
  • ras-GRF1 / metabolism*

Substances

  • Catenins
  • Cell Adhesion Molecules
  • Phosphoproteins
  • Rasgrf1 protein, mouse
  • ras-GRF1
  • Threonine
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • GTP Phosphohydrolases
  • Delta Catenin