Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion

Cell Rep. 2015 Sep 8;12(10):1618-30. doi: 10.1016/j.celrep.2015.08.002. Epub 2015 Aug 28.


Synaptic adhesion molecules regulate diverse aspects of synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3(-/-)) mice display markedly reduced excitatory synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3(-/-) mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates excitatory synapse development and locomotion behavior.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Animals
  • Cell Differentiation
  • Excitatory Postsynaptic Potentials
  • Exons
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Learning
  • Locomotion
  • Membrane Glycoproteins
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules / physiology*
  • Neuronal Plasticity
  • Protein Isoforms / physiology
  • Psychomotor Performance
  • RNA Splice Sites
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
  • Synapses / physiology*
  • Synaptic Transmission


  • Lrfn4 protein, mouse
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • Protein Isoforms
  • RNA Splice Sites
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2