Calsyntenins function as synaptogenic adhesion molecules in concert with neurexins

Cell Rep. 2014 Mar 27;6(6):1096-1109. doi: 10.1016/j.celrep.2014.02.010. Epub 2014 Mar 6.

Abstract

Multiple synaptic adhesion molecules govern synapse formation. Here, we propose calsyntenin-3/alcadein-β as a synapse organizer that specifically induces presynaptic differentiation in heterologous synapse-formation assays. Calsyntenin-3 (CST-3) is highly expressed during various postnatal periods of mouse brain development. The simultaneous knockdown of all three CSTs, but not CST-3 alone, decreases inhibitory, but not excitatory, synapse densities in cultured hippocampal neurons. Moreover, the knockdown of CSTs specifically reduces inhibitory synaptic transmission in vitro and in vivo. Remarkably, the loss of CSTs induces a concomitant decrease in neuron soma size in a non-cell-autonomous manner. Furthermore, α-neurexins (α-Nrxs) are components of a CST-3 complex involved in CST-3-mediated presynaptic differentiation. However, CST-3 does not directly bind to Nrxs. Viewed together, these data suggest that the three CSTs redundantly regulate inhibitory synapse formation, inhibitory synapse function, and neuron development in concert with Nrxs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Differentiation / physiology
  • Female
  • HEK293 Cells
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism
  • Pregnancy
  • Synapses / metabolism
  • Synaptic Transmission

Substances

  • CLSTN3 protein, human
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • Clstn3 protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins