Selected SALM (synaptic adhesion-like molecule) family proteins regulate synapse formation

J Neurosci. 2010 Apr 21;30(16):5559-68. doi: 10.1523/JNEUROSCI.4839-09.2010.

Abstract

Synaptic cell adhesion molecules regulate various steps of synapse formation. Despite the great diversity of neuronal synapses, relatively few adhesion molecules with synaptogenic activity have been identified. Synaptic adhesion-like molecules (SALMs) are members of a family of cell adhesion molecules known to regulate neurite outgrowth and synapse maturation; however, the role of SALMs in synapse formation remains unknown. We found that expression of the SALM family proteins SALM3 and SALM5 in nonneural and neural cells induces both excitatory and inhibitory presynaptic differentiation in contacting axons. SALM3 and SALM5 proteins are enriched in synaptic fractions, and form strong (SALM3) or weak (SALM5) complexes with postsynaptic density-95 (PSD-95), an abundant postsynaptic scaffolding protein at excitatory synapses. Aggregation of SALM3, but not SALM5, on dendritic surfaces induces clustering of PSD-95. Knockdown of SALM5 reduces the number and function of excitatory and inhibitory synapses. These results suggest that selected SALM family proteins regulate synapse formation, and that SALM3 and SALM5 may promote synapse formation through distinct mechanisms.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Communication / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / genetics
  • Gene Knockdown Techniques
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Humans
  • Inhibitory Postsynaptic Potentials / genetics
  • Membrane Glycoproteins
  • Mice
  • Multigene Family / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / physiology*
  • Neural Inhibition / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology
  • Rats
  • Synapses / genetics
  • Synapses / physiology*

Substances

  • Cell Adhesion Molecules
  • Lrfn4 protein, mouse
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules