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

Abstract

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. SALM3 is a postsynaptic adhesion molecule known to regulate synapse development, but the underlying mechanism remains unclear. Li et al. find that SALM3 interacts with presynaptic LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) in a splicing-dependent manner. In addition, they show that SALM3-mutant mice display reduced excitatory synapse number and hypoactivity. © 2015 The Authors