Interaction between telencephalin and ERM family proteins mediates dendritic filopodia formation

J Neurosci. 2007 Aug 15;27(33):8866-76. doi: 10.1523/JNEUROSCI.1047-07.2007.

Abstract

Dendritic filopodia are long, thin, actin-rich, and dynamic protrusions that are thought to play a critical role as a precursor of spines during neural development. We reported previously that a telencephalon-specific cell adhesion molecule, telencephalin (TLCN) [intercellular adhesion molecule-5 (ICAM-5)], is highly expressed in dendritic filopodia, facilitates the filopodia formation, and slows spine maturation. Here we demonstrate that TLCN cytoplasmic region binds ERM (ezrin/radixin/moesin) family proteins that link membrane proteins to actin cytoskeleton. In cultured hippocampal neurons, phosphorylated active forms of ERM proteins are colocalized with TLCN in dendritic filopodia, whereas alpha-actinin, another binding partner of TLCN, is colocalized with TLCN at surface membranes of soma and dendritic shafts. Expression of constitutively active ezrin induces dendritic filopodia formation, whereas small interference RNA-mediated knockdown of ERM proteins decreases filopodia density and accelerates spine maturation. These results indicate the important role of TLCN-ERM interaction in the formation of dendritic filopodia, which leads to subsequent synaptogenesis and establishment of functional neural circuitry in the developing brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dendrites / ultrastructure*
  • Diagnostic Imaging / methods
  • Embryo, Mammalian
  • Hippocampus / cytology
  • Immunoprecipitation / methods
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Models, Biological
  • Mutation / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Protein Binding
  • Pseudopodia / physiology*
  • Surface Plasmon Resonance / methods
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection / methods
  • Two-Hybrid System Techniques

Substances

  • Actins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Icam5 protein, mouse
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • ezrin