Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2

Biochem Biophys Res Commun. 2009 Jun 19;384(1):55-60. doi: 10.1016/j.bbrc.2009.04.069. Epub 2009 Apr 23.

Abstract

Rap small GTPases regulate excitatory synaptic strength and morphological plasticity of dendritic spines. Changes in spine structure are mediated by the F-actin cytoskeleton, but the link between Rap activity and actin dynamics is unclear. Here, we report a novel interaction between SPAR, a postsynaptic inhibitor of Rap, and alpha-actinin, a family of actin-cross-linking proteins. SPAR and alpha-actinin engage in bidirectional structural plasticity of dendritic spines: SPAR promotes spine head enlargement, whereas increased alpha-actinin2 expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and alpha-actinin2 can function in an additive rather than antagonistic fashion at the same dendritic spine, generating combination spine/filopodia hybrids. These data identify a molecular pathway bridging the actin cytoskeleton and Rap at synapses, and suggest that formation of spines and filopodia are not necessarily opposing forms of structural plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actinin / genetics
  • Actinin / metabolism*
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Dendritic Spines / metabolism
  • Dendritic Spines / physiology*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Pseudopodia / metabolism
  • Pseudopodia / physiology*
  • Rats
  • Two-Hybrid System Techniques

Substances

  • E6-target protein 1
  • GTPase-Activating Proteins
  • Actinin