p120 catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins

Neuron. 2006 Jul 6;51(1):43-56. doi: 10.1016/j.neuron.2006.05.018.

Abstract

Both the cadherin-catenin complex and Rho-family GTPases have been shown to regulate dendrite development. We show here a role for p120 catenin (p120ctn) in regulating spine and synapse formation in the developing mouse brain. p120catenin gene deletion in hippocampal pyramidal neurons in vivo resulted in reduced spine and synapse densities along dendrites. In addition, p120 catenin loss resulted in reduced cadherin levels and misregulation of Rho-family GTPases, with decreased Rac1 and increased RhoA activity. Analyses in vitro indicate that the reduced spine density reflects aberrant Rho-family GTPase signaling, whereas the effects on spine maturation appear to result from reduced cadherin levels and possibly aberrant Rho-family GTPase signaling. Thus, p120ctn acts as a signal coordinator between cadherins and Rho-family GTPases to regulate cytoskeletal changes required during spine and synapse development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / embryology*
  • Brain / growth & development
  • Cadherins / metabolism*
  • Catenins
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Differentiation / genetics
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Down-Regulation / genetics
  • Gene Deletion
  • Hippocampus / cytology
  • Hippocampus / embryology
  • Hippocampus / growth & development
  • Male
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism
  • Signal Transduction / physiology
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism
  • rho GTP-Binding Proteins / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Cadherins
  • Catenins
  • Cell Adhesion Molecules
  • Phosphoproteins
  • delta catenin
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein