Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin

Neuron. 2003 Jan 23;37(2):263-74. doi: 10.1016/s0896-6273(02)01168-6.

Abstract

The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK. Overexpression of dominant-negative EphB receptor, catalytically inactive kalirin, or dominant-negative Rac1, or inhibition of PAK eliminates ephrin-induced spine development. This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Carrier Proteins*
  • Cells, Cultured
  • Dendrites / drug effects*
  • Dendrites / ultrastructure
  • Guanine Nucleotide Exchange Factors / physiology*
  • Hippocampus / cytology
  • Hippocampus / embryology*
  • Humans
  • Indicators and Reagents
  • Morphogenesis
  • Neuronal Plasticity / physiology
  • Phosphorylation
  • Receptors, Eph Family / physiology*
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction / physiology
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Tissue Fixation
  • Transfection
  • rac1 GTP-Binding Protein / physiology

Substances

  • Carrier Proteins
  • Guanine Nucleotide Exchange Factors
  • Indicators and Reagents
  • Kalrn protein, rat
  • Rho Guanine Nucleotide Exchange Factors
  • Receptors, Eph Family
  • rac1 GTP-Binding Protein