Role of beta-catenin in synaptic vesicle localization and presynaptic assembly

Neuron. 2003 Nov 13;40(4):719-31. doi: 10.1016/s0896-6273(03)00718-9.

Abstract

Cadherins and catenins are thought to promote adhesion between pre and postsynaptic elements in the brain. Here we show a role for beta-catenin in localizing the reserved pool of vesicles at presynaptic sites. Deletion of beta-catenin in hippocampal pyramidal neurons in vivo resulted in a reduction in the number of reserved pool vesicles per synapse and an impaired response to prolonged repetitive stimulation. This corresponded to a dispersion of vesicles along the axon in cultured neurons. Interestingly, these effects are not due to beta-catenin's involvement in cadherin-mediated adhesion or wnt signaling. Instead, beta-catenin modulates vesicle localization via its PDZ binding domain to recruit PDZ proteins such as Veli to cadherin at synapses. This study defines a specific role for cadherins and catenins in synapse organization beyond their roles in mediating cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Electric Stimulation
  • Fetus
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Protein Structure, Tertiary / physiology
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / ultrastructure
  • Rats
  • Synaptic Membranes / metabolism
  • Synaptic Membranes / ultrastructure
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Vesicular Transport Proteins
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cadherins
  • Carrier Proteins
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Lin7a protein, mouse
  • Trans-Activators
  • Vesicular Transport Proteins
  • beta Catenin